Tinidazole clinical pharmacology
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ahmed Zaghw, M.D. [2]
Clinical Pharmacology
Mechanism of Action
Tinidazole is an antiprotozoal, antibacterial agent.
Pharmacokinetics
Absorption After oral administration, tinidazole is rapidly and completely absorbed. A bioavailability study of Tindamax tablets was conducted in adult healthy volunteers. All subjects received a single oral dose of 2 g (four 500 mg tablets) of Tindamax following an overnight fast. Oral administration of four 500 mg tablets of Tindamax under fasted conditions produced a mean peak plasma concentration (Cmax) of 47.7 (±7.5) µg/mL with a mean time to peak concentration (Tmax) of 1.6 (±0.7) hours, and a mean area under the plasma concentration-time curve (AUC, 0-∞) of 901.6 (± 126.5) µg/hr/mL at 72 hours. The elimination half-life (T1/2) was 13.2 (±1.4) hours. Mean plasma levels decreased to 14.3 µg/mL at 24 hours, 3.8 µg/mL at 48 hours and 0.8 µg/mL at 72 hours following administration. Steady-state conditions are reached in 2½ - 3 days of multi-day dosing.
Administration of Tindamax tablets with food resulted in a delay in Tmax of approximately 2 hours and a decline in Cmax of approximately 10%, compared to fasted conditions. However, administration of Tindamax with food did not affect AUC or T1/2 in this study.
In healthy volunteers, administration of crushed Tindamax tablets in artificial cherry syrup, [prepared as described in Dosage and Administration (2.2)] after an overnight fast had no effect on any pharmacokinetic parameter as compared to tablets swallowed whole under fasted conditions.
Distribution Tinidazole is distributed into virtually all tissues and body fluids and also crosses the blood-brain barrier. The apparent volume of distribution is about 50 liters. Plasma protein binding of tinidazole is 12%. Tinidazole crosses the placental barrier and is secreted in breast milk.
Metabolism Tinidazole is significantly metabolized in humans prior to excretion. Tinidazole is partly metabolized by oxidation, hydroxylation, and conjugation. Tinidazole is the major drug-related constituent in plasma after human treatment, along with a small amount of the 2-hydroxymethyl metabolite.
Tinidazole is biotransformed mainly by CYP3A4. In an in vitro metabolic drug interaction study, tinidazole concentrations of up to 75 µg/mL did not inhibit the enzyme activities of CYP1A2, CYP2B6, CYP2C9, CYP2D6, CYP2E1, and CYP3A4.
The potential of tinidazole to induce the metabolism of other drugs has not been evaluated.
Elimination The plasma half-life of tinidazole is approximately 12-14 hours. Tinidazole is excreted by the liver and the kidneys. Tinidazole is excreted in the urine mainly as unchanged drug (approximately 20-25% of the administered dose). Approximately 12% of the drug is excreted in the feces.
Patients with impaired renal function: The pharmacokinetics of tinidazole in patients with severe renal impairment (CrCL < 22 mL/min) are not significantly different from the pharmacokinetics seen in healthy subjects. However, during hemodialysis, clearance of tinidazole is significantly increased; the half-life is reduced from 12.0 hours to 4.9 hours. Approximately 43% of the amount present in the body is eliminated during a 6-hour hemodialysis session. The pharmacokinetics of tinidazole in patients undergoing routine continuous peritoneal dialysis have not been investigated.
Patients with impaired hepatic function: There are no data on tinidazole pharmacokinetics in patients with impaired hepatic function. Reduction of metabolic elimination of metronidazole, a chemically-related nitroimidazole, in patients with hepatic dysfunction has been reported in several studies.[1]
References
Adapted from the FDA Package Insert.