Effects of acute febrile infectious diseases on the oral pharmacokinetics and effects of nitrendipine enantiomers and of bisoprolol.
In 2 longitudinal studies with 10 patients each, the stereoselective pharmacokinetics of nitrendipine and the pharmacokinetics of racemic (rac) bisoprolol (both 20mg orally) were investigated during acute febrile infectious diseases and at least 6 weeks later in the healthy state. The area under the plasma concentration-time curve (AUC) and peak plasma concentration (Cmax) of rac-nitrendipine were increased in the infectious state by 89% [95% confidence interval (CI): 24 to 187%] and 95% (95% CI: 22 to 209%), respectively. Similar increases were observed for both S- and R-nitrendipine. Nitrendipine exhibited stereoselective pharmacokinetics in both the healthy state and the infectious state, but the mean ratios of S:R AUC values [healthy: 1.79 (95% CI: 1.36 to 2.11); infectious: 1.87 (95% CI: 1.62 to 2.11)] were not different. The elimination half-life, protein binding and haemodynamic effects of nitrendipine also did not differ between the infectious and the healthy state. The mechanism for the disease effects may be related to suppression of hepatic cytochrome P450 activity by mediators of inflammatory reactions. On the other hand, none of the pharmacokinetic parameters, including nonrenal clearance, of rac-bisoprolol was changed during febrile infectious disease, indicating specificity in the effects of acute febrile disease on oxidative drug metabolism.
Division of Pharmacology, Center for Bio-Pharmaceutical Sciences, Leiden University, The Netherlands.
P A
PA
Soons
C
C
Grib
D D
DD
Breimer
W
W
Kirch
D000208:Acute Disease; D000319:Adrenergic beta-Antagonists / Q000493:pharmacokinetics*; D000328:Adult; D000368:Aged; D017298:Bisoprolol; D001831:Body Temperature; D003141:Communicable Diseases / Q000150:complications / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005260:Female; D005334:Fever / Q000209:etiology / Q000378:metabolism; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009568:Nitrendipine / Q000493:pharmacokinetics*; D011412:Propanolamines / Q000493:pharmacokinetics*; D013237:Stereoisomerism
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D003577:Cytochrome P-450 Enzyme System; D009568:Nitrendipine; D017298:Bisoprolol