Pharmacokinetics Of Rifampicin Research Articles

Enzyme induction by rifampicin and its time-dependent pharmacokinetics

Pharmacokinetics and enzyme induction effects of rifampicin, an antituberculosis, were studied on 8 female and 2 male patients. Rifampicin (450 mg) was administered orally every morning before breakfast over a period of 8 weeks. On the 1st, 14th, 21st, 28th and 56th days of treatment, venous blood samples were drawn immediately, 2, 4 and 8 h after the administration of rifampicin. Rifampicin level in the serum was determined by high-performance liquid chromatography. Determination of rifampicin level was made in duplicate. Data of rifampicin levels in the serum (Ct) were calculated with a personal computer. Biexponential equation, Ct=A (e-Kat-e-Ket), and the pharmacokinetic parameters were non linear least squares regression analysis. The first-pass effect was obtained from calculated by the method of Gibaldi et al. Cmax and area under blood concentration curve gradually decreased until the 21st day of treatment and, thereafter, reached a steady-state until the 56th day of treatment. Biological half-life fluctuated until the 28th day of treatment and reached steady-state on day 28. Vd, Cl and first-pass effects showed a definite increase until the 21st day of treatment. After that, they reached a steady-state until the 56th day of treatment. In summary, pharmacokinetics of rifampicin was found to be time-dependent and closely related to the enzyme inducibility of the drug.

Pharmacokinetics of rifampicin and desacetylrifampicin in tuberculous patients after different rates of infusion.

Four rates of rifampicin infusion ranging from 3.3 to 15 mg/min in 12 tuberculous patients were studied. Blood samples (n = 10) were drawn during infusion and 8 h later. Urine samples were collected in six fractions during a 24-h period. Rifampicin and desacetylrifampicin were measured by high-pressure liquid chromatography. Results show that the maximum plasma concentrations increase linearly for each dose with the rate of infusion, and that the amounts excreted in the urines are highly dependent on the administered dose. Simulation of plasma concentrations after different dosage regimens shows that a double rate of infusion--20 mg min-1 during 1 h and then 200 mg h-1--allows plasma concentrations to be quickly reached and maintained at a 20 mg L-1 level, far higher than the minimum inhibitory concentrations of most germs.

Pharmacokinetic studies of rifampicin in the elderly.

The pharmacokinetics of rifampicin (RMP) and its principal active metabolite desacetylrifampicin (DA-RMP) were studied in six subjects, ranging in age from 78 to 95 years, after single oral doses of 10 mg/kg RMP. The maximal plasma concentrations (Cmax) and the elimination half-lives (t 1/2 beta) of RMP are 8.83 +/- 1.72 mg L-1 and 4.09 +/- 2.59 h, respectively. They are comparable to those reported in young adults. The same applies to the Cmax value (1.93 +/- 0.53 mg L-1) and t 1/2 beta value (4.65 +/- 2.61 h) of DA-RMP. However, the renal clearance of RMP (0.0075 +/- 0.0036 L h-1) and the amounts of RMP (20.7 +/- 9.9 mg) and DA-RMP (13.3 +/- 5.6 mg) excreted in the urine during a 24-h period are lower than those reported in young adults. The renal excretion of RMP and DA-RMP, therefore, is reduced in the elderly. But since the drug is also excreted through the liver to such an extent that serum levels are the same as in young adults, for therapeutic purposes the metabolism of RMP may be globally considered as unaltered in elderly patients.

Clinical Pharmacokinetics of Rifampicin

After oral administration on an empty stomach, the absorption of rifampicin (rifampin) is rapid and practically complete. With a single 600mg dose, peak serum concentration of the order of 10microgram/ml generally occur 2 hours after administration. The half-life of rifampicin for this dose level is of the order of 2.5 hours. The amount of rifampicin extracted by the liver during its first passage through the hepatoportal system and transferred to bile is relevance for the time course of distribution of the antibiotic in the blood compartment. With dose of the order of 300 to 450mg, the excretory capacity of the liver for the antibiotic is saturated. As a consequence, increasing the dose of antibiotic results in a more than proportional increase in serum concentrations. On repeated administration, and most likely as a consequence of self-induced (autoinduction) metabolism, the rate of disappearance of rifampicin from the blood compartment increases in the early phase of treatment, the phenomenon affecting mainly the levels following the peak, with a consequent reduction in half-life. Approximately 80% of rifampicin is transported in blood bound to plasma proteins, mainly albumin. Rifampicin is well distributed, although to a different degree, in the various tissues of the human body. Probably in the hepatocyte, rifampicin undergoes a process of desacetylation. The metabolic derivative, desacetylrifampicin, is more polar than the parent compound, and microbiologically active. This metabolite accounts for the majority of the antibacterial activity in the bile Rifampicin is almost equally excreted in the bile and urine, the recovery in the 2 fluids being of the same order of magnitude. Administration of rifampicin to newborn infants and children is followed by blood levels generally lower than those found in adults for the same dose levels. In patients with impaired liver and kidney function the elimination of the antibiotic from the blood compartment is slower than in normal subjects. Rifampicin has been found to compete with bilirubin and other cholefil substances for biliary excretion, giving rise to transient and reversible increased bilirubin and BSP retention values. A kinetic model study on the transfer constants between various body compartments has indicated that rifampicin is rapidly absorbed from the intestine and that the absorption rate increases with time. Rifampicin as such is transferred into urine at a rate 3 times higher than the rate of transfer into bile. Desacetylrifampicin, the more polar metabolic derivative of rifampicin, behaves in the opposite way since its rate of transfer into bile is 4 times higher than that into urine. The rate of biotransformation of rifampicin into desacetylrifampicin is of the same order of magnitude as than of biotransformation of the latter into a further metabolic derivative, which could be a glucuronide conjugate...