Nitazoxanide 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
Absorption: Following oral administration of Alinia Tablets or Oral Suspension, maximum plasma concentrations of the active metabolites tizoxanide and tizoxanide glucuronide are observed within 1-4 hours. The parent nitazoxanide is not detected in plasma. Pharmacokinetic parameters of tizoxanide and tizoxanide glucuronide are shown in Tables 1 and 2below.
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Alinia for Oral Suspension is not bioequivalent to Alinia Tablets. The relative bioavailability of the suspension compared to the tablet was 70%.
Effect of Food: When Alinia Tablets are administered with food, the AUCt of tizoxanide and tizoxanide glucuronide in plasma is increased almost two-fold and the Cmax is increased by almost 50%.
When Alinia for Oral Suspension was administered with food, the AUCt of tizoxanide and tizoxanide glucuronide increased by about 45-50% and the Cmax increased by ≤10%.
Alinia Tablets and for Oral Suspension were administered with food in clinical trials and hence they are recommended to be administered with food.
Multiple dosing: Following oral administration of a single Alinia Tablet every 12 hours for 7 consecutive days, there was no significant accumulation of nitazoxanide metabolites tizoxanide or tizoxanide glucuronide detected in plasma.
Distribution: In plasma, more than 99% of tizoxanide is bound to proteins.
Metabolism: Following oral administration in humans, nitazoxanide is rapidly hydrolyzed to an active metabolite, tizoxanide (desacetyl-nitazoxanide). Tizoxanide then undergoes conjugation, primarily by glucuronidation. In vitrometabolism studies have demonstrated that tizoxanide has no significant inhibitory effect on cytochrome P450 enzymes.
Elimination: Tizoxanide is excreted in the urine, bile and feces, and tizoxanide glucuronide is excreted in urine and bile. Approximately two-thirds of the oral dose of nitazoxanide is excreted in the feces and one-third in the urine.
Special Populations
Patients with Impaired Hepatic and/or Renal Function: The pharmacokinetics of nitazoxanide in patients with impaired hepatic and/or renal function has not been studied.
Geriatric Patients: The pharmacokinetics of nitazoxanide in geriatric patients has not been studied.
Pediatric Patients: The pharmacokinetics of nitazoxanide following administration of Alinia Tablets in pediatric patients less than 12 years of age has not been studied. The pharmacokinetics of nitazoxanide following administration of Alinia for Oral Suspension in pediatric patients less than 1 year of age has not been studied.[1]
References
Adapted from the FDA Package Insert.