Chemical formula: C₁₀H₁₃N₃O₅S Molecular mass: 287.29 g/mol PubChem compound: 6842999
Nifurtimox is an antiprotozoal drug.
Nifurtimox exposure-response relationships and the time course of pharmacodynamics response are unknown.
At the recommended dose, nifurtimox treatment does not result in large mean increases (>20 ms) in the QTc interval.
The mean (CV) nifurtimox AUC estimates ranged between 1676-2670 µg∙h/L (19–32) and Cmax estimates ranged between 425-568 µg/L (26–50%) following administration of single dose 120 mg nifurtimox with food in adult Chagas patients. No clinically significant differences in nifurtimox AUC or Cmax at the 120 mg dose were observed when using two tablet strengths (30 and 120 mg) or administered as whole or dissolved tablets under fed conditions. The median time to reach maximum concentration (Tmax) of nifurtimox under fed conditions was 4 hours (range: 2 to 8 hours).
Following administration of a single oral dose of 120 mg in adult Chagas patients, nifurtimox Cmax increased 68%, AUC increased 71%, and Tmax increased by 1 hour with a high-fat meal (800–1000 calorie, approximately 60% fat) compared to fasted conditions.
Nifurtimox passes the blood brain barrier as well as the placental barrier. The plasma proteins binding of nifurtimox is 42%.
The mean (CV) estimates for elimination half-life of nifurtimox ranged between 2.4–3.6 hours (12–37).
Metabolism of nifurtimox is primarily mediated via nitroreductases. Exploratory investigations identified two major pharmacologically inactive metabolites (M-4, M-6) and several other minor metabolites in pooled human plasma. M-4 is a rearranged cysteine conjugate of nifurtimox with a half-life of approximately 28 hours, and M-6 is postulated to be formed by hydrolytic cleavage of the hydrazone moiety with a half-life of approximately 10 hours.
Following administration of nifurtimox under fed and fasted conditions, approximately 44% and 27% of the dose was recovered in urine mainly as metabolites, respectively. Biliary and fecal elimination of nifurtimox and its metabolites has not been evaluated.
The effect of renal or hepatic impairment on the pharmacokinetics of nifurtimox is unknown. Blood concentrations of nifurtimox increased in patients with ESRD.
No clinical studies evaluating the drug interaction potential of nifurtimox have been conducted.
Cytochrome P450 Enzymes (CYPs): Nifurtimox is not a substrate of CYPs. Nifurtimox and its metabolites (M-4 or M-6) are not inhibitors or inducers of CYPs.
Transporter Systems: Nifurtimox is not a substrate or inhibitor of P-glycoprotein (P-gp) or breast cancer resistant protein (BCRP), and is not an inhibitor of organic anion transporting polypeptide (OATPs), multidrug and toxin extrusion (MATE) proteins (MATE1/MATE2-K), organic anion transporter ⅓ (OAT1/OAT3), or organic cation transporter 2 (OCT2). Major metabolites (M-4 or M-6) of nifurtimox are not inhibitors of P-gp, BCRP, OATPs, MATE1, MATE2K, OAT1, OAT3, or OCT2 at clinically relevant concentrations.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
