The influence of posture on the pharmacokinetics of orally administered nifedipine.
1. Nifedipine (20 mg as capsules) and soluble paracetamol (1 g) were co-administered to eight healthy young volunteers on three separate occasions, following which in random order they stood, lay on their left side or lay on their right side for 4 h. 2. The time to maximum plasma concentration of paracetamol was significantly lower when standing or lying on the right side compared with recumbent left, indicating more rapid gastric emptying. 3. The times to maximum plasma concentrations of nifedipine and its metabolite produced at first pass were reduced when standing or lying on the right side. These postures were associated with significantly higher peak plasma concentrations and AUC values of nifedipine but not of its nitropyridine metabolite. 4. The increase in heart rate following nifedipine administration was significantly greater when lying on the right side compared with the left. 5. The data are consistent with transient saturation of first pass metabolism of nifedipine with postures which favour rapid gastric emptying. The results demonstrate the importance of defining the precise posture in studies in which pharmacokinetic and pharmacodynamic measurements are made on drugs which are absorbed rapidly and are subject to presystemic elimination.
Renwick
A G
AG
Clinical Pharmacology Group, University of Southampton, Bassett Crescent East.
Ahsan
C H
CH
Challenor
V F
VF
Daniels
R
R
Macklin
B S
BS
Waller
D G
DG
George
C F
CF
D000082:Acetaminophen / Q000493:pharmacokinetics; D000284:Administration, Oral; D000328:Adult; D005260:Female; D005746:Gastric Emptying; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D009543:Nifedipine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011187:Posture
D000082:Acetaminophen; D009543:Nifedipine