Dosing time and sex-related differences in the pharmacokinetics of cefodizime and in the circadian cortisol rhythm.
Two g cefodizime i.v. administration at 00:00, 06:00, 12:00 and 18:00 respectively, to 8 male and 8 female, young healthy volunteers, has shown: 1. a sex-related difference in both plasma (AUC) and total cumulative excretion of the agent with larger values in females than in males; 2. a dosing time-related difference in plasma (AUC) with the largest values for Rx at 00:00 and lowest for Rx at 18:00 in both males and females; 3. a dosing time-related difference in urinary concentration of cefodizime with largest values for Rx at 06:00 and lowest for Rx at 12:00. These urinary changes were highly correlated with changes in AUC for each dosing time; 4. no dosing time-related changes were observed for plasma T1/2 as well as cumulative urinary excretion of cefodizime; 5. curve patterns of plasma cortisol had similar aspects for both control and Rx at 00:00 with no sex-related differences. Curve patterns differed from control for other dosing times (p less than 0.005 to p less than 0.001 with ANOVA tests).
Pharma Bio-Research International Institute for Clinical Pharmacology, Assen, The Netherlands.
J H
JH
Jonkman
A
A
Reinberg
B
B
Oosterhuis
O E
OE
de Noord
F A
FA
Kerkhof
Y
Y
Motohashi
F
F
Levi
F
F
Dammacco
F
F
Carandente
D000328:Adult; D002439:Cefotaxime / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D002940:Circadian Rhythm; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D007275:Injections, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D012737:Sex Factors
D002439:Cefotaxime; D006854:Hydrocortisone; C033356:cefodizime