[Correlation between pharmacokinetic parameters of rifampicin and its biologically active metabolite as related to estimation of the relative bioavailability of the antibiotic].
In the bioavailability studies with drugs biotransformed to biologically active metabolities only the concentrations of the parent drug (PD) are usually taken into account even when the pharmacokinetic data on the metabolite(s) (M) are available. However, such data may be useful as an alternative source for the bioavailability determination. Moreover, the clinical outcomes often depend on both the PD and M concentrations. The aim of the study performed with two rifampicin formulations, tablets and dragee, was to correlate the pharmacokinetic parameters of the PD and 25-O-deacetylrifampicin, a microbiologically active M of rifampicin, and to examine whether the bioavailability parameters based on the PD and M concentrations were compatible. The serum concentrations of the PD and M were determined in 8 healthy volunteers by HPLC. Despite different patterns of the PD and M pharmacokinetic profiles the PD peak concentration (Cmax) and especially the AUC correlated with Cmax or the AUC of the M (r = 0.76 and 0.92 respectively). Moreover, the extent of the absorption expressed as the AUC ratio for the PD correlated with the AUC ratio for the M (r = 0.86). However, neither the time to reach the maximum (tmax), nor the Cmax/AUC ratio, a measure of the absorption rate, based on the PD pharmacokinetic data correlated with the respective parameters calculated with using the M concentrations. Thus, only the estimates of the extent of the absorption and not of the absorption rate based on the PD and M data may be considered as compatible.
Firsov
A A
AA
Dombrovskiĭ
V S
VS
Kadenatsi
I B
IB
Gagaeva
E V
EV
Strachunskiĭ
L S
LS
D000904:Antibiotics, Antitubercular / Q000493:pharmacokinetics*; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D008297:Male; D012016:Reference Values; D012293:Rifampin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics*
D000904:Antibiotics, Antitubercular; C032393:25-deacetylrifampicin; D012293:Rifampin
Vzaimosviaz' mezhdu parametrami farmakokinetiki rifampitsina i ego biologicheski aktivnogo metabolita v kontekste otsenki otnositel'noĭ biodostupnosti antibiotika.