[Effects of rifampicin on the pharmacokinetics of doxycycline].
Because of the potential of doxycycline-rifampicin for oral therapy of infectious diseases with intracellular bacteria, specially brucellosis and the well known cytochrome P450 enzyme system inductive activity of rifampicin, we may speculate that this antibiotic can altered the serum concentration-time profile of doxycycline when given in combination. So, the main pharmacokinetic parameters of doxycycline (200 mg/day orally) in seven patients before and after rifampicin association (10 mg/kg/day). According to the results two groups may be individualized: the first (n = 3) showed no variation in the doxycycline++ pharmacokinetic; the second (n = 4) had significant differences (p less than 0.05) for all pharmacokinetic parameters (AUC, T1/2, Cl, Cmax) after association with rifampicin (AUC were half reduced). Moreover, as regard doxycycline half-life, a difference was observed between these two groups before rifampicin treatment: in one case T1/2 was of 17.9 + 6.6 hours, while in the other it was of 9.2 + 2.3 hours. The group with obvious enzyme induction had the longer half life. This suggests that the inductive rifampicin effect would be essentially observed in patients considered as "poor metabolizers". The pharmacokinetic modifications observed are likely of clinical significance on account of the doxycycline serum concentrations decrease under the MIC of most agents of intracellular infections.
Garraffo
R
R
Laboratoire de Pharmacologie, Faculté de Médecine, Nice.
Dellamonica
P
P
Fournier
J P
JP
Lapalus
P
P
Bernard
E
E
Beziau
H
H
Chichmanian
R M
RM
D000328:Adult; D004318:Doxycycline / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D012293:Rifampin / Q000008:administration & dosage / Q000494:pharmacology*
D004318:Doxycycline; D012293:Rifampin
Effet de la rifampicine sur la pharmacocinétique de la doxycycline.