Transdermal delivery of mepindolol and propranolol in normal man. 1st communication: study design, clinical and pharmacodynamic aspects.
In the present study the beta-adrenoreceptor blocking effects of acute and repeated transdermally delivered mepindolol (20 mg/9.8 cm2 patch) and propranolol (40 mg/9.8 cm2 patch) on supine and stimulated circulatory function (isoprenaline infusion, isometric hand grip, delayed auditory feed-back) in nine healthy male volunteers were assessed. The study was conducted in a placebo-controlled double-blind cross-over fashion, with three one-week treatment courses randomly allocated in a period-balanced fashion. Treatment phases were separated by a one-week wash-out phase. The placebo and mepindolol patch were well tolerated, whereas the propranolol patch caused skin irritation and itching in most subjects, and even vesicular lesions in 3/9 subjects. Acute and repeated 24 h application of the propranolol patch caused only small and clinically not relevant changes of heart rate and blood pressure. Acute application of the mepindolol patch induced only mild blunting of the diastolic blood pressure and heart rate responses to isoprenaline i.v. infusion at 8 h. However, the isoprenaline responses were nearly abolished after one week repeated 24 h application of the mepindolol patch, in a stable and protracted fashion. The circulatory responses to isometric handgrip and delayed auditory feedback tended to be reduced, but to a smaller extent than for the isoprenaline test. Repeated application of mepindolol via the investigational device for transdermal drug delivery (BIO TSD) thus resulted in stable and protracted beta-adrenoreceptor blockade.
de Mey
C
C
SK & F-Institute for Applied Clinical Pharmacology, Göttingen, Fed. Rep. of Germany.
Enterling
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D
Ederhof
M
M
Wesche
H
H
Osterwald
H
H
D000279:Administration, Cutaneous; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D000328:Adult; D004311:Double-Blind Method; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D010869:Pindolol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D011433:Propranolol / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; C015340:mepindolol; D011433:Propranolol; D010869:Pindolol