PHARMACOKINETIC CHARACTERIZATION OF TRANSDERMAL DELIVERY SYSTEMS

被引:96
作者
BERNER, B
JOHN, VA
机构
[1] Ciba-Geigy Corporation, Ardsley, New York, 10502-2699
关键词
D O I
10.2165/00003088-199426020-00005
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The key aspects of the pharmacokinetics of transdermal delivery systems including time lag, steady-state plasma levels and decline phase are illustrated in this review. The 7 currently marketed transdermal systems [nitroglycerin (glyceryl trinitrate), estradiol, clonidine, fentanyl, nicotine, scopolamine (hyoscine) and estradiol/norethisterone acetate] are discussed, as are systems in development. Single-dose absolute bioavailability studies characterise the period of onset, the steady-state plateau and the declining phase, and typify transdermal delivery. More complex temporal profiles result from interactions with enhancers or removal of the system before steady-state conditions are achieved. Clinically these systems are used to achieve multiple peak serum estradiol concentrations after application of transdermal estradiol, and an initial peak systemic concentration of testosterone after application of transdermal testosterone. Multiple-dose, dose proportionality and skin site bioequivalence studies are needed for the full pharmacokinetic characterisation of a transdermal delivery system. The relationship of system design to variability is discussed. Although the data are limited, population factors, cutaneous metabolism and tolerance all appear to influence the disposition of drugs administered transdermally. For example, the route of delivery influences which nitroglycerin metabolite predominates. Futhermore, as a result of tolerance to nitrates, a transdermal delivery system must be removed for 8 to 12 hours for optimal effect. Therefore, transdermal delivery systems, designed on the basis of pharmacokinetic principles and concentration-effect relationships, have the potential to provide optimal therapy for the treatment of some conditions.
引用
收藏
页码:121 / 134
页数:14
相关论文
共 68 条
[1]  
ABELIN T, 1989, METHOD FIND EXP CLIN, V11, P205
[2]   TRANSDERMAL TESTOSTERONE THERAPY IN THE TREATMENT OF MALE HYPOGONADISM [J].
AHMED, SR ;
BOUCHER, AE ;
MANNI, A ;
SANTEN, RJ ;
BARTHOLOMEW, M ;
DEMERS, LM .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1988, 66 (03) :546-551
[3]   PHARMACOKINETICS AND PHARMACODYNAMICS OF TRANSDERMALLY ADMINISTERED CLONIDINE [J].
ARNDTS, D ;
ARNDTS, K .
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY, 1984, 26 (01) :79-85
[4]   STABLE ISOTOPE METHOD FOR STUDYING TRANSDERMAL DRUG ABSORPTION - THE NICOTINE PATCH [J].
BENOWITZ, NL ;
CHAN, K ;
DENARO, CP ;
JACOB, P .
CLINICAL PHARMACOLOGY & THERAPEUTICS, 1991, 50 (03) :286-293
[5]   ASYMPTOTIC SOLUTION FOR NONSTEADY-STATE DIFFUSION THROUGH OIL-WATER MULTILAMINATES [J].
BERNER, B ;
COOPER, ER .
JOURNAL OF MEMBRANE SCIENCE, 1983, 14 (02) :139-145
[6]   A TRANSDERMAL NICOTINE SYSTEM - FEASIBILITY STUDIES [J].
BERNER, B ;
MAZZENGA, GC ;
GARGIULO, PM ;
STEFFENS, R .
JOURNAL OF CONTROLLED RELEASE, 1992, 20 (01) :13-19
[7]   ETHANOL WATER MUTUALLY ENHANCED TRANSDERMAL THERAPEUTIC SYSTEM .2. SKIN PERMEATION OF ETHANOL AND NITROGLYCERIN [J].
BERNER, B ;
MAZZENGA, GC ;
OTTE, JH ;
STEFFENS, RJ ;
JUANG, RH ;
EBERT, CD .
JOURNAL OF PHARMACEUTICAL SCIENCES, 1989, 78 (05) :402-407
[8]  
Berner B., 1992, TREATISE CONTROLLED, P1
[9]  
BERNER B, 1987, TRANSDERMAL DELIVERY, V2, P133
[10]   IMPROVING COMPLIANCE IN AN INNER-CITY HYPERTENSIVE PATIENT POPULATION [J].
BRANCHE, GC ;
BATTS, JM ;
DOWDY, VM ;
FIELD, LS ;
FRANCIS, CK .
AMERICAN JOURNAL OF MEDICINE, 1991, 91 :S37-S41