Transdermal delivery of mepindolol and propranolol in normal man. 2nd communication: pharmacokinetic and neuro-endocrine aspects.
The plasma and urinary pharmacokinetics of mepindolol and propranolol were assessed in nine healthy volunteers after single and 1-week daily repeated application of the drugs by a novel transdermal delivery system (BIO TSD). Qualitatively, the time courses of the plasma concentrations for both compounds were similar and indicative of effective drug input. On the first day of the treatment courses plasma levels rose slowly, reaching their observed maximum after 24 h. The latter still was in the rising phase of the curve and further input on longer application is likely. After 1 week daily repeated application apparent steady state conditions were reached. The plasma concentrations were low in comparison to the levels reported for oral dosing. Only small amounts of unchanged drug were excreted via urine. The effects of the investigational treatments on supine-resting and stimulated neuroendocrine variables were assessed also. A blunting of the adrenaline response to delayed auditory feed-back mental stress testing (DAF) was consistently observed after propranolol, but not after mepindolol. Noradrenaline responses to DAF were not altered. No consistent effects were observed in terms of the adrenaline responses to 3 min isometric handgrip testing (IHG). Noradrenaline responses to IHG were slightly blunted, relative to placebo on the first day when propranolol and mepindolol were applied. This was probably related to the usually high responses to placebo as reference. At the end of 1 week repeated application of the patches mean supine resting plasma renin activity (PRA) was significantly reduced by propranolol but not by mepindolol, and the mean PRA responses to 5 min i.v. infusion of isoprenaline was reduced by both.
de Mey
C
C
SK&F-Institute for Applied Clinical Pharmacology, Göttingen, Fed. Republic of Germany.
Meineke
I
I
Enterling
D
D
Rehbock
C
C
Osterwald
H
H
D000279:Administration, Cutaneous; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000328:Adult; D002395:Catecholamines / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D009490:Neurosecretory Systems / Q000187:drug effects*; D010869:Pindolol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D011433:Propranolol / Q000008:administration & dosage* / Q000493:pharmacokinetics; D012083:Renin / Q000097:blood
D000319:Adrenergic beta-Antagonists; D002395:Catecholamines; C015340:mepindolol; D011433:Propranolol; D010869:Pindolol; D012083:Renin