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Clinical Pharmacokinetics of Clonidine

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Summary

Clonidine is a centrally active antihypertensive agent effective in the treatment of mild, moderate and severe hypertension, alone or in combination with other drugs. Use of oral clonidine has often been limited by side effects which include dry mouth and drowsiness. Transdermal clonidine was therefore developed as an alternative to oral therapy.

Ideally, a drug administered at a constant rate into the systemic circulation should attain steady-state concentrations with less peak-to-trough fluctuation than that associated with intermittent oral dosing. In theory, transdermal administration should thus minimise the adverse effects associated with peak plasma drug concentration, while avoiding the potential for decreased efficacy associated with trough levels.

Clonidine has been incorporated into a small, pliable adhesive cutaneous delivery device designed to provide therapeutically effective doses of drug at a constant rate for at least 7 days. The transdermal therapeutic system is a laminate consisting of an external film impermeable to moisture and to the drug, a thin layer of active drug dispersed within a highly drug-permeable matrix, a membrane with a controlled intrinsic permeability regulating the rate of delivery of drug to the skin, and an adhesive coating that attaches the system to the skin surface. The permeation of drug through the skin occurs primarily by diffusion.

Application of the clonidine transdermal system to both normotensive and hypertensive subjects has consistently reduced systolic and diastolic blood pressures. Maximum reduction in blood pressure occurs 2 to 3 days after initial application, and is maintained for at least 7 days or until the system is removed. The rate at which clonidine is presented to the skin surface is controlled by the microporous membrane: this rate is the same for all strengths of transdermal clonidine, the amount of clonidine released being proportional to its surface area. Thus, the daily dose is regulated by the area of skin covered. Typically, steady-state plasma concentrations are reached on the fourth day after initial transdermal system application. The lack of dose dependency in half-life and renal clearance estimates emphasise that the transdermal absorption of clonidine is linear. The plasma clonidine concentration produced by a particular transdermal dose varies considerably between individuals as a result of interindividual variation in renal clearance. For this reason, it is recommended that dosages be titrated up from the smallest system (3.5cm2) until the desired pharmacological effect has been obtained.

Blood pressure returns to pretreatment values over 3 to 4 days after removal of the transdermal system. Because the decline in plasma clonidine concentrations is slower following cessation of transdermal delivery than with oral therapy, rebound hypertension which has been observed in some patients upon abrupt cessation of high doses of oral clonidine does not appear to be a problem with discontinuing transdermal clonidine therapy.

Blood pressure control with the transdermal clonidine system has been demonstrated to be equal to or in some cases better than that achieved with oral clonidine. Side effects associated with oral clonidine have been reported to be substantially reduced or eliminated in many patients. Additionally, once weekly transdermal clonidine dosing offers the potential for improved patient compliance.

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References

  • Algren JJ, Rodgers C. Hypertension associated with clonidine. Veterinary and Human Toxicology 26: 32–35, 1984

    PubMed  Google Scholar 

  • Anavekar SN, Jarrott B, Toscano M, Louis WJ. Pharmacokinetic and pharmacodynamic studies of oral clonidine in normotensive subjects. European Journal of Clinical Pharmacology 23: 1–5, 1982

    PubMed  CAS  Google Scholar 

  • Anderson FJ, Gambertoglio JG, Shrier RW. Clinical use of drugs in renal failure. Charles C. Thomas, Springfield, 1975

    Google Scholar 

  • Arndts D. New aspects of the pharmacokinetics and pharmacodynamics of clonidine in man. Chest 83: 397–400, 1983

    PubMed  CAS  Google Scholar 

  • Arndts D, Arndts K. Pharmacokinetics and pharmacodynamics of transdermally administered clonidine. European Journal of Clinical Pharmacology 26: 79–85, 1984

    PubMed  CAS  Google Scholar 

  • Arndts D, Doevendans J, Kirsten R, Heintz B. New aspects of the pharmacokinetics and pharmacodynamics of clonidine in man. European Journal of Clinical Pharmacology 24: 21–30, 1983

    PubMed  CAS  Google Scholar 

  • Arndts D, Stahle H, Forster HJ. Development of a RIA for clonidine and its comparison with the reference methods. Journal of Pharmacological Methods 6: 295–307, 1981

    PubMed  CAS  Google Scholar 

  • Arndts D, Stahle H, Struck CJ. A newly developed precise and sensitive radioimmunoassay for clonidine. Arzneimittel-Forschung 29: 532–538, 1979

    PubMed  CAS  Google Scholar 

  • Artman M, Boerth RC. Clonidine poisoning: a complex problem. American Journal of Diseases of Children 137: 171–174, 1983

    PubMed  CAS  Google Scholar 

  • Bennett WM, Muther RS, Parker RA. Drug therapy in renal failure: dosing guidelines for adults. Annals of Internal Medicine 93: 286–325, 1980

    PubMed  CAS  Google Scholar 

  • Berner B. Pharmacokinetics of transdermal drug delivery. Journal of Pharmaceutical Sciences 74: 718–721, 1985

    PubMed  CAS  Google Scholar 

  • Bjornsson TD. Nomogram for drug dosage adjustment in patients with renal failure. Clinical Pharmacokinetics 11: 164–170, 1986

    PubMed  CAS  Google Scholar 

  • Bock KD, Merguet P, Heimsoth VH. Effect of clonidine on regional blood flow and its use in the treatment of hypertension. In Onesti G et al. (Eds) Hypertension mechanisms and management, pp. 395–403, Grune & Stratton, New York, 1973

    Google Scholar 

  • Boekhorst JC, Lustermans FATH, van Tol RGL. Transdermal administration of clonidine for treatment of mild-to-moderate essential hypertension. Current Therapeutic Research 41: 215–225, 1987

    Google Scholar 

  • Boekhorst JC, van Tol RGL. Catapres transdermal therapeutic system (TTS) for long-term treatment of hypertension. In Weber et al. (Eds) Low dose oral and transdermal therapy of hypertension, pp. 122–125, Steinkopff, Darmstadt, 1985

    Google Scholar 

  • Brest AN. Hemodynamic and cardiac effects of clonidine. Journal of Cardiovascular Pharmacology 2: S39–S46, 1980

    PubMed  Google Scholar 

  • Brodde OE, Daul A. Alpha and beta-adrenoceptor changes in patients on maintenance hemodialysis. Contributions to Nephrology 41: 99–107, 1984

    PubMed  CAS  Google Scholar 

  • Burris JF, Mroczek WJ. Transdermal administration of clonidine: a new approach to antihypertensive therapy. Pharmacotherapy 6: 30–34, 1986

    PubMed  CAS  Google Scholar 

  • Byyny RL, Culbertson VL, Levine SS, Loverde ML, Mitchell WD. Oral clonidine loading combined with transdermal clonidine in essential hypertension. Clinical Research 35: 439, 1987

    Google Scholar 

  • Campesi VM, Massry SG. Effects of acute and chronic treatment with clonidine. Chest 83: 380–382, 1983

    Google Scholar 

  • Chandrasekaran SK, Bayne W, Shaw JE. Pharmacokinetics of drug permeation through human skin. Journal of Pharmaceutical Sciences 67: 1370–1374, 1978

    PubMed  CAS  Google Scholar 

  • Chandrasekaran SK, Darda S, Michaels AS, Cleary GW. US Patent 4,201,211; Assigned to Alza Corporation and Boehringer Ingelheim GmbH, Germany, May 6, 1980

    Google Scholar 

  • Chandrasekaran SK, Shaw JE. Design of transdermal therapeutic systems. Contemporary Topics in Polymer Science 2: 291–308, 1977

    CAS  Google Scholar 

  • Chu LC, Bayne WF, Tao FT, Schmitt LG, Shaw JE. Determination of submicrogram quantities of clonidine in biological fluids. Journal of Pharmaceutical Sciences 68: 72–74, 1979

    PubMed  CAS  Google Scholar 

  • Cohen IM, O’Connor DT, Preston RA. Reduced renovascular resistance by clonidine. Clinical Pharmacology and Therapeutics 26: 572–577, 1979

    PubMed  CAS  Google Scholar 

  • Darda S, Forster HJ, Stahle HJ. Metabolischer abbau von clonidin. Arzneimittel-Forschung 28: 255–259, 1978

    PubMed  CAS  Google Scholar 

  • Davies DS, Baille TA, Neill E, Hughes H, Davies DL. Applications of stable isotope labelling in studies of the pharmacokinetics and metabolism of clonidine. Advances in Pharmacology and Therapeutics: Proceedings of the Seventh International Congress on Pharmacology 7: 215–223, 1979

    CAS  Google Scholar 

  • Davies DS, Wing LMH, Reid JL, Neill E, Tippett P, et al. Pharmacokinetics and concentration effect relationships of intravenous and oral clonidine. Clinical Pharmacology and Therapeutics 21: 593–601, 1977

    PubMed  CAS  Google Scholar 

  • Dollery CT, Davies DS, Draffan GH, Dargie HJ, Dean CR, et al. Clinical pharmacology and pharmacokinetics of clonidine. Clinical Pharmacology and Therapeutics 19: 11–17, 1976

    PubMed  CAS  Google Scholar 

  • Domino LE, Domino SE, Stockstill MS. Relationship between plasma concentrations of clonidine and mean arterial pressure during an accidental clonidine overdose. British Journal of Clinical Pharmacology 21: 71–74, 1986

    PubMed  CAS  Google Scholar 

  • Drayer JIM, Weber MA. Current concepts in the evaluation and treatment of patients with mild to moderate hypertension. Hospital Formulary 18: 164–170, 1983

    Google Scholar 

  • Edlund PO. Determination of clonidine in human plasma by glass capillary/gas chromatography with electron-capture detection. Journal of Chromatography 187: 161–169, 1980

    PubMed  CAS  Google Scholar 

  • Falkner B, Lowenthal DT, Thanki B. Transcutaneous clonidine in the treatment of adolescent hypertension. Journal of Hypertension 3: 561–563, 1985

    Google Scholar 

  • Farina PR, Homon CA, Chow CT, Keirns JJ, Zavorskas PA, et al. Radioimmunoassay for clonidine in human plasma and urine using a solid phase second antibody separation. Therapeutic Drug Monitoring 7: 344–350, 1985

    PubMed  CAS  Google Scholar 

  • Fillastre JP, Dubois D, Brunelle P. Plasma half-life of 14C-clonidine in normal and uraemic patients. In New aspects for the treatment of arterial hypertension, pp. 81–85, Boehringer Ingelheim, Florence, 1973

    Google Scholar 

  • Flynn GL, Yalkowsky SH, Roseman TJ. Mass transport phenomena and models: theoretical concepts. Journal of Pharmaceutical Sciences 63: 479–510, 1974

    PubMed  CAS  Google Scholar 

  • Frisk-Holmberg M, Edlund PO, Paalzow L. Pharmacokinetics of clonidine and its relation to the hypotensive effect in patients. British Journal of Clinical Pharmacology 6: 227–232, 1978

    PubMed  CAS  Google Scholar 

  • Frisk-Holmberg M, Paalzow L, Edlund PO. Clonidine kinetics in man: evidence for dose dependency and changed pharmacokinetics during chronic therapy. British Journal of Clinical Pharmacology 12: 653–658, 1981

    PubMed  CAS  Google Scholar 

  • Frisk-Holmberg M, Paalzow L, Wibell L. Relationship between the cardiovascular effects and steady-state kinetics of clonidine in hypertension. European Journal of Clinical Pharmacology 26: 309–313, 1984

    PubMed  CAS  Google Scholar 

  • Frohlich ED. Initial therapy for hypertension. Hospital Practice: May 15; 89–96, 1987

    Google Scholar 

  • Gilchrest B. Bullous dermatosis of hemodialysis. Annals of Internal Medicine 83: 480–483, 1975

    PubMed  CAS  Google Scholar 

  • Golub MS, Thananopavarn C, Sambhi MP. Transdermal clonidine in elderly patients with mild hypertension: effects on blood pressure and plasma catecholamines. In Weber et al. (Eds) Low dose oral and transdermal therapy of hypertension, pp. 16–21, Steinkopff, Darmstadt, 1985

    Google Scholar 

  • Green S, Zawada ET, Muakkassan AN, Johnson M, Mackenzie T, et al. Effect of clonidine therapy on renal hemodynamics in renal transplant hypertension. Archives of Internal Medicine 144: 1205–1208, 1984

    PubMed  CAS  Google Scholar 

  • Greenleaf JE, Montgomery LD, Brock PJ, van Beaumont W. Limb blood flow: rest and heavy exercise in sitting and supine positions in man. Aviation, Space and Environmental Medicine 50: 702–707, 1979

    CAS  Google Scholar 

  • Groth H, Vetter H, Knusel J, Foerster E, Siegenthaler W, et al. Transdermal clonidine application: long-term results in essential hypertension. Klinische Wochenschrift 62: 925–930, 1984

    PubMed  CAS  Google Scholar 

  • Guthrie Jr GP. Diabetes and hypertension: clonidine monotherapy. In Weber et al. (Eds) Low dose oral and transdermal therapy of hypertension, pp. 39, Steinkopff Verlag, Darmstadt, 1984

    Google Scholar 

  • Guthrie GP, Miller RE, Kotchen TA. Clonidine in patients with diabetes and mild hypertension. Clinical Pharmacology and Therapeutics 34: 713–717, 1983

    PubMed  Google Scholar 

  • Guy RH, Hadgraft J. Pharmacokinetics interpretation of the plasma levels of clonidine following transdermal delivery. Journal of Pharmaceutical Sciences 74: 1016–1018, 1985

    PubMed  CAS  Google Scholar 

  • Guyton AC. Basic human physiology: normal function and mechanisms of disease, p. 202, WB Saunders Co., Philadelphia, 1971

    Google Scholar 

  • Hadeland H, Dymlin JF, Hokfelt B. The effect of insulin induced hypoglycemia on plasma renin activity and urinary catecholamines before and following clonidine in man. Acta Endocrinology 71: 321–330, 1972

    Google Scholar 

  • Haeusler G. Studies on the possible contribution of a peripheral presynaptic action of clonidine and dopamine to their vascular effects under in vivo conditions. Naunyn-Schmeideberg’s Archives of Pharmacology 295: 191–202, 1976

    CAS  Google Scholar 

  • Hartikainen-Sorri AL, Heikkinen JE, Koivisto M. Pharmacokinetics of clonidine during pregnancy and nursing. Obstetrics & Gynecology 69: 598–600, 1987

    CAS  Google Scholar 

  • Heckner RM. Systematische Untersuchungen zur proteinbindung biologisch wirksamer Substanzen. Pharmatherapeutica 2: 177–186, 1979

    CAS  Google Scholar 

  • Hogan MJ, Wallin JD, Chu L. Plasma clonidine concentration and pharmacologic effect. Clinical Pharmacology and Therapeutics 30: 729–734, 1981

    PubMed  CAS  Google Scholar 

  • Holzer H, Ziak E, Sterz F. Oral versus transdermal clonidine application in hypertension treatment. In Abstracts of the sympathetic nervous system in the pathogenesis: complications and treatment of hypertension. Satellite Symposium, European Meeting on Hypertension, Milan, Italy, 1985

  • Hopkins K, Aarons L, Rowland M. Absorption of clonidine from a transdermal therapeutic system when applied to different body sites. In Weber & Mathias (Eds) Mild hypertension: proceedings of the international Titisee workshop, pp. 143–147, Steinkopff Verlag, Darmstadt, 1984

    Google Scholar 

  • Hopkins K, Aarons L, Rowland M. Absorption and excretion of clonidine following application of Catapres-TTS to different skin sites. In Weber et al. (Eds) Low dose oral and transdermal therapy of hypertension, pp. 134–137, Steinkopff Verlag, Darmstadt, 1985

    Google Scholar 

  • Hossmann V, Specht T. Clonidine in depressed kidney function. In Hayduk & Bock (Eds) Central blood pressure regulation: the role of alpha2-receptor stimulation, pp. 101–112, Steinkopff Verlag, Darmstadt, 1983

    Google Scholar 

  • Houston MC. Abrupt cessation of treatment in hypertension: consideration of clinical features, mechanisms, prevention and management of the discontinuation syndrome. American Heart Journal 102: 415–430, 1981

    PubMed  CAS  Google Scholar 

  • Houston MC. Clonidine hydrochloride. Southern Medical Journal 75(6): 713–721, 1982

    PubMed  CAS  Google Scholar 

  • Hughes H, Baille TA. Synthesis of clonidine and 1,3-dimethyl-clonidine labelled at specific positions with deuterium and carbon-13. Journal of Labelled Compounds and Radiopharmaceuticals 17: 871–888, 1980

    CAS  Google Scholar 

  • Hulter HN, Licht JH, Flnicki LP, Singh S. Clinical efficacy and pharmacokinetics of clonidine in hemodialysis and renal insufficiency. Journal of Laboratory and Clinical Medicine 94: 223–231, 1979

    PubMed  CAS  Google Scholar 

  • Isaac L. Clonidine in the central nervous system: site and mechanism of hypotensive action. Journal of Cardiovascular Pharmacology 2(1): S5–S19, 1980

    PubMed  Google Scholar 

  • Itskovitz HD. Clonidine and the kidney. Journal of Cardiovascular Pharmacology 2: S47–S60, 1980

    PubMed  Google Scholar 

  • Jeunemaitre X, Ged E, Ducrocq MB, Alhenc-Gelas F, Corvol P. Effects of transdermal clonidine in young and elderly patients with mild hypertension: evaluation by 3 non invasive methods of blood pressure measurement. Journal of Cardiovascular Pharmacology 10: 162–167, 1987

    PubMed  CAS  Google Scholar 

  • Kanto J, Allonen H, Hiltunen R, Marvola M, Mantyla R. Bioavailability and clinical effects of three brands of clonidine: the relationship between plasma level and effect. International Journal of Clinical Pharmacology, Therapeutics and Toxicology 20: 118–121, 1982

    CAS  Google Scholar 

  • Kaufman WC, Jowett D, Ruthmansdorfer K. Diurnal variations in thermoregulatory functions. Federation Proceedings 32 (3, part 1): 39, 1973

    Google Scholar 

  • Keranen A, Nykanen S, Tashinen J. Pharmacokinetics and side-effects of clonidine. European Journal of Clinical Pharmacology 13: 97–101, 1978

    PubMed  CAS  Google Scholar 

  • Kersh ES, Kronfield SJ, Unger A, Popper RW, Contor S, et al. Autonomic insufficiency in uremia as a cause of hemodialysis induced hypotension. New England Journal of Medicine 290: 650–653, 1974

    PubMed  CAS  Google Scholar 

  • Klein C, Morton N, Kelley S, Metz S. Transdermal clonidine therapy in elderly mild hypertensives: effects on blood pressure, plasma norepinephrine and fasting plasma glucose. Journal of Hypertension 3: S81–S84, 1985

    PubMed  CAS  Google Scholar 

  • Kobinger W. Central alpha-adrenergic systems as targets for hypotensive drugs. Reviews in Physiology and Biochemical Pharmacology 81: 39–100, 1978

    CAS  Google Scholar 

  • Kobinger W, Walland A. Circulation studies with 2-(2, 6-di-chlorophenylamino)-2-imidazoline hydrochloride, Arzneimittel-Forschung 17: 292–300, 1967

    PubMed  CAS  Google Scholar 

  • Kolloch R, Finster H, Overlack A, Muller HM, Stumpe KO. Low dose oral and transdermal application of clonidine in mild hypertension: hemodynamic and biochemical correlates. In Weber et al. (Eds) Low dose oral and transdermal therapy of hypertension, pp. 71–80, Steinkopff, Darmstadt, 1985

    Google Scholar 

  • Langley MS, Heel RC. Transdermal clonidine. A preliminary review of its pharmacodynamic properties and therapeutic efficacy. Drugs 35: 123–142, 1988

    PubMed  CAS  Google Scholar 

  • Louis WJ, Anavekar MB, Conway EL, Jarrott B. Relationship of immunoassayable clonidine plasma levels to its pharmacologic action in clinical and experimental hypertension. Chest 83: 352–353, 1983

    PubMed  CAS  Google Scholar 

  • Lowenthal DT. Pharmacokinetics of clonidine. Journal of Cardiovascular Pharmacology 2: 521–537, 1980

    Google Scholar 

  • Lowenthal DT, Affrime MB, Meyer A, Kim K, Falkner B, et al. Pharmacokinetics and pharmacodynamics of clonidine in varying states of renal function. Chest 83s: 386s–390s, 1983

    Google Scholar 

  • Lowenthal DT, Paran E, Saris SD, Bies C, Falkner B. The use of transdermal clonidine in the hypertensive patient with chronic renal failure. Clinical Pharmacology and Therapeutics, in press, 1988

    Google Scholar 

  • Lowenthal DT, Saris SD, Falkner B, Porter RS, Haratz A, et al. Pharmacodynamics and pharmacokinetics of oral and trans-dermal clonidine in chronic renal insufficiency. In Weber et al. (Eds) Low dose oral and transdermal therapy of hypertension, pp. 86–92, Steinkopff, Darmstadt, 1985

    Google Scholar 

  • Lowenthal DT, Saris S, Paran E, Cristal N, Sharif K, et al. Efficacy of clonidine, a transdermal therapeutic system: the international clinical trial experience. American Heart Journal 112: 893–900, 1986a

    PubMed  CAS  Google Scholar 

  • Lowenthal DT, Saris SD, Porter RS, Bies C, Falkner B. Pharmacokinetics and pharmacodynamics of transdermal clonidine in renal insufficiency. Journal of Hypertension 4: 5576, 1986b

    Google Scholar 

  • MacGregor TR, Matzek KM, Keirns JJ, Van Wayjen RGM, Van-den Ende A, et al. Pharmacokinetics of transdermally delivered clonidine. Clinical Pharmacology and Therapeutics 38: 278–284, 1985a

    PubMed  CAS  Google Scholar 

  • MacGregor TR, Relihan GL, Keirns JJ. Pharmacokinetics or oral sustained release clonidine in humans. Arzneimittel-Forschung 35: 440–446, 1985b

    PubMed  CAS  Google Scholar 

  • Magorien RD, Hermiller JB, Unverferth DV, Leier CV. Regional hemodynamic effects of clonidine in congestive heart failure. Journal of Cardiovascular Pharmacology 7: 91–96, 1985

    PubMed  CAS  Google Scholar 

  • Manhem P, Paalzow L, Hokfelt B. Plasma clonidine in relation to blood pressure catecholamines, and renin activity during long-term treatment of hypertension. Clinical Pharmacology and Therapeutics 31: 445–451, 1982

    PubMed  CAS  Google Scholar 

  • McMahon FG, Michael R, Jain A, Ryan JR. Clinical experience with clonidine TTS. In Weber & Mathias (Eds) Mild hypertension, pp. 148–152, Steinkopff, Darmstadt, 1984

    Google Scholar 

  • Mitchell HC, Pettinger WA. Dose-response of clonidine on plasma catecholamines in the hypernoradrenergic state associated with vasodilator β-blocker therapy. Journal of Cardiovascular Pharmacology 3: 647–654, 1981

    PubMed  CAS  Google Scholar 

  • Mroczek WJ. Preliminary evaluation of transdermal clonidine administration in hypertensive patients receiving a diuretic. In Beck KD (Ed) Catapres (Clonidine): pathways in the development of a pharmaceutical, pp. 126–132, Edition Cantor, Aulendork, 1983

    Google Scholar 

  • Mroczek WJ, Davidov M, Finnerty FA. Intravenous clonidine in hypertensive patients. Clinical Pharmacology and Therapeutics 14: 847–851, 1973

    PubMed  CAS  Google Scholar 

  • Muir AL, Burton JL, Lawrie DM. Circulatory effects at rest and exercise of clonidine, an imidazoline derivative with hypotensive properties. Lancet 2: 181–184, 1969

    PubMed  CAS  Google Scholar 

  • Murray S, Waddell KA, Davies DS. Plasma and urine by combined gas chromatography/mass spectrometry with ammonia chemical ionization. Biomedical Mass Spectrometry 8: 500–502, 1981

    PubMed  CAS  Google Scholar 

  • Niarchos AP, Baerl L, Radichievich I. Role of renin and aldosterone suppression in the antihypertensive mechanism of clonidine. American Journal of Medicine 65: 614–618, 1978

    PubMed  CAS  Google Scholar 

  • Nies A, Robertson D, Stone WJ. Hemodialysis hypotension is not the result of uremic peripheral autonomic neuropathy. Journal of Laboratory and Clinical Medicine 94: 395–402, 1979

    PubMed  CAS  Google Scholar 

  • Onesti G, Schwartz AB, Kim KE, PazMartinez V, Schwartz C. Antihypertensive effect of clonidine. Circulation Research 28–29 (Suppl. II): 53–69, 1971

    Google Scholar 

  • Onesti G, Schwartz AB, Kim KE, Schwartz C, Brest AM. Pharmacodynamic effects of a new antihypertensive drug, Catapres (ST-155). Circulation 39: 219–228, 1969

    PubMed  CAS  Google Scholar 

  • Paran E, Saris SD, Lowenthal DT, Falkner B, Sharif K, et al. The transition from oral to transdermal clonidine in varying degrees of renal function. Clinical Pharmacology and Therapeutics 37: 220, 1985

    Google Scholar 

  • Pettinger WA. Pharmacology of clonidine. Journal of Cardiovascular Pharmacology 2: S21–S28, 1980

    PubMed  Google Scholar 

  • Pettinger WA, Keeton TK, Campbell WB. Evidence for a renal α-adrenergic receptor inhibiting renin release. Circulation Research 38: 338–346, 1976

    PubMed  CAS  Google Scholar 

  • Pickering T, Gribbin B, Oliver DO. Baroreflex sensitivity in patients on long term hemodialysis. Clinical Sciences 43: 645–665, 1972

    CAS  Google Scholar 

  • Popli S, Daugirdas JT, Ing TS, Neubauer JA, Hockenberry B, et al. A double-blind placebo-controlled trial of transdermal clonidine in mild hypertension. Circulation 72 (Suppl. III): 12, 1985

    Google Scholar 

  • Popli S, Daugirdas JT, Ing TS, Neubauer JA, Hockenberry B, et al. Transdermal clonidine in mild hypertension: a randomized, double-blind, placebo-controlled trial. Archives of Internal Medicine 146: 2140–2144, 1986

    PubMed  CAS  Google Scholar 

  • Popli S, Stroka TS, Ing JT, Daugirdas JT, Norvsis MJ, et al. Transdermal clonidine for hypertensive patients. Clinical Therapeutics 5: 624–628, 1983

    PubMed  CAS  Google Scholar 

  • Reid JL, Wing LMH, Mathias CJ, Frankel HL, Neill E. The central hypotensive effect of clonidine. Clinical Pharmacology and Therapeutics 21: 375–381, 1977

    PubMed  CAS  Google Scholar 

  • Romoff MS, Campese VM, Lane K, Massry SG. Mechanism of autonomic dysfunction in uremia: evidence for reduced end organ response to norepinephrine. Kidney International 14: 731–739, 1978

    Google Scholar 

  • Rosenthal SP. Uremic dermatitis. Archives of Dermatology and Syphilology 23: 934–945, 1931

    Google Scholar 

  • Roskos KV, Guy RH, Maibach HI. Percutaneous absorption in the aged. Dermatologic Clinics 4: 455–465, 1986

    PubMed  CAS  Google Scholar 

  • Rowell LB. Human cardiovascular adjustments to exercise and thermal stress. Physiological Reviews 54: 75–159, 1974

    PubMed  CAS  Google Scholar 

  • Rudd P, Blaschke TF. Antihypertensive drugs and the drug therapy of hypertension. In Gilman et al. (Eds) The pharmacologic basis of therapeutics, 7th ed., pp. 784–805, MacMillan, New York, 1985

    Google Scholar 

  • Saris SD, Lowenthal DT, Haratz A, Packer J, Porter RS, et al. Pharmacodynamics of oral and transdermal clonidine in varying degrees of renal function. Clinical Research 32: 699A, 1984

    Google Scholar 

  • Schaller MD, Nussberger J, Waeber B, Porchet M, Brunner HR. Transdermal clonidine therapy in hypertensive patients. Journal of the American Medical Association 253: 233–235, 1985

    PubMed  CAS  Google Scholar 

  • Schaller MD, Waeber B, Nussberger J, Brunner HR. Transdermal administration of clonidine in hypertensive patients. European Heart Journal 51: 104, 1984

    Google Scholar 

  • Scoggins RB, Harlan Jr WR. Cutaneous manifestations of hyperlipidemia and uraemia. Postgraduate Medicine 41: 537–545, 1967

    PubMed  CAS  Google Scholar 

  • Shaw JE. Pharmacokinetics of nitroglycerin and clonidine delivered by the transdermal route. American Heart Journal 108: 217–223, 1984

    PubMed  CAS  Google Scholar 

  • Shaw JE, Chandrasekaran SK. Transdermal therapeutic systems. In Prescott & Nimmo (Eds) Drug absorption, pp. 186–193, ADIS Press, New York, 1979

    Google Scholar 

  • Shaw JE, Enscore D, Chu L. Clonidine rate-controlled system: technology and kinetics. In Weber & Mathias (Eds) Mild hypertension. Proceedings of the international Titisee workshop. pp. 134–142, Steinkopff Verlag, Darmstadt, 1984

    Google Scholar 

  • Stephenson LA, Wenger CB, O’Donovan BH, Nadel ER. Arcadian rhythm in sweating and cutaneous blood flow. American Journal of Physiology 246 (3, part 2): R321–R324, 1984

    PubMed  CAS  Google Scholar 

  • Sung PK, Samet P, Yeh BK. Effects of clonidine and chlorthalidone on blood pressure and glucose tolerance in hypertensive patients. Current Therapeutics Research 13: 280–285, 1971

    CAS  Google Scholar 

  • Thananopavarn C, Golub MS, Eggena P, Barrett JD, Sambhi MP. Clonidine, a centrally acting sympathetic inhibitor, as mono-therapy for mild to moderate hypertension. American Journal of Cardiology 49: 153–158, 1982

    PubMed  CAS  Google Scholar 

  • Velasquez MT, Rho J, Maronde RF, Barr J. Plasma clonidine levels in hypertension. Clinical Pharmacology and Therapeutics 34: 341–346, 1983

    PubMed  CAS  Google Scholar 

  • Wallin JD, Krane NK, Bergman S, Morgan M. The use of trans-cutaneous clonidine hydrochloride in patients with diabetes mellitus and mild hypertension. Journal of Clinical Hypertension 4: 315–321, 1985

    Google Scholar 

  • Weber MA. Discontinuation syndrome following cessation of treatment with clonidine and other antihypertensive agents. Journal of Cardiovascular Pharmacology 2: 573–589, 1980

    Google Scholar 

  • Weber MA. Transdermal antihypertensive therapy: clinical and metabolic considerations. American Heart Journal 112: 906–912, 1986

    PubMed  CAS  Google Scholar 

  • Weber MA, Case DB, Baer L, Sealey JE, Drayer JIM, et al. Renin and aldosterone suppression in the antihypertensive action of clonidine. American Journal of Cardiology 38: 825–830, 1976

    PubMed  CAS  Google Scholar 

  • Weber MA, Drayer J. Clinical experience with rate-controlled delivery of antihypertensive therapy by a transdermal system. American Heart Journal 108: 231–236, 1984

    PubMed  CAS  Google Scholar 

  • Weber MA, Drayer J, McMahon FG, Hamburger R, Shah AR, et al. Transdermal administration of clonidine for treatment of high blood pressure. Archives of Internal Medicine 144: 1211–1213, 1984a

    PubMed  CAS  Google Scholar 

  • Weber MA, Drayer JIM, Lipson JL, Brewer DD. Clinical effectiveness of the transdermal route of antihypertensive treatment. In Weber & Mathias (Eds) Mild hypertension: current controversies and new approaches, pp. 153–158, Steinkopff Verlag, Darmstadt, 1984c

    Google Scholar 

  • Weber MA, Drayer J, Brewer DD, Lipson JL. Transdermal continuous antihypertensive therapy. Lancet 1: 9–11, 1984b

    PubMed  CAS  Google Scholar 

  • Wing LMH, Reid JL, Davies DS, Neill EAM, Tippett P, et al. Pharmacokinetic and concentration effect relationships of clonidine in essential hypertension. European Journal of Clinical Pharmacology 12: 463–469, 1977

    PubMed  CAS  Google Scholar 

  • Wood RA. The therapeutic uses of clonidine. Scottish Medical Journal 24: 226–232, 1979

    PubMed  CAS  Google Scholar 

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  1. Department of Geriatrics and Adult Development and Department of Pharmacology, Mt Sinai School of Medicine, New York, USA

    D. T. Lowenthal, K. M. Matzek & T. R. MacGregor

  2. Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, USA

    D. T. Lowenthal, K. M. Matzek & T. R. MacGregor

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  1. D. T. Lowenthal
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  2. K. M. Matzek
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  3. T. R. MacGregor
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Lowenthal, D.T., Matzek, K.M. & MacGregor, T.R. Clinical Pharmacokinetics of Clonidine. Clin-Pharmacokinet 14, 287–310 (1988). https://doi.org/10.2165/00003088-198814050-00002

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  • DOI: https://doi.org/10.2165/00003088-198814050-00002

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