title: Biowaiver monographs for immediate release solid oral dosage forms: pyrazinamide.
abstract: Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing pyrazinamide as the only active pharmaceutical ingredient (API) are reviewed. Pyrazinamide is BCS Class III, with linear absorption over a wide dosing range. The risk of bioinequivalence is estimated to be low. Depending on the definition used, pyrazinamide can be classified as a narrow therapeutic index (NTI) drug, which is usually a caveat to biowaiving but may be deemed acceptable if the Summary of Product Characteristics (SmPCs) of the test product stipulates the need for regular monitoring of liver function. It is concluded that a biowaiver can be recommended for IR solid oral dosage only when the test product (a) contains only excipients present in pyrazinamide IR solid oral drug products approved in ICH or associated countries, (b) these excipients are present in amounts normally used in IR solid oral dosage forms, (c) the test product is very rapidly dissolving, (d) the SmPC of the test product indicates the need for monitoring of the patient's liver function.
authors.affiliation: Institute of Pharmaceutical Technology, JW Goethe University, Frankfurt, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Becker
authors.forename: J B
authors.initials: JB
authors.lastname: Dressman
authors.forename: G L
authors.initials: GL
authors.lastname: Amidon
authors.forename: H E
authors.initials: HE
authors.lastname: Junginger
authors.forename: S
authors.initials: S
authors.lastname: Kopp
authors.forename: K K
authors.initials: KK
authors.lastname: Midha
authors.forename: V P
authors.initials: VP
authors.lastname: Shah
authors.forename: S
authors.initials: S
authors.lastname: Stavchansky
authors.forename: D M
authors.initials: DM
authors.lastname: Barends
mesh_terms: D000284:Administration, Oral; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D001682:Biological Availability; D005079:Excipients; D006801:Humans; D011718:Pyrazinamide / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D012995:Solubility; D013607:Tablets; D013810:Therapeutic Equivalency
chemical_list: D000995:Antitubercular Agents; D005079:Excipients; D013607:Tablets; D011718:Pyrazinamide