title: Comparison of bovine in vivo bioavailability of two sulfamethazine oral boluses exhibiting different in vitro dissolution profiles.
abstract: The bolus (or oblet) is a dosage form that can be used for the oral administration of pharmaceutical compounds to ruminating species. Unlike traditional tablets, oral boluses may contain quantities of drug on the order of grams rather than milligrams. Due to its size, it is only recently that USP-like in vitro dissolution methods have been developed for this dosage form. However, whether or not these dissolution tests can predict product in vivo performance has yet to be determined. The importance of this issue is apparent when the U.S. Food and Drug Administration Center for Veterinary Medicine is faced with the decision of whether to require additional in vivo bioequivalence study data to support the approval of changes in product chemistry or manufacturing method. The current study was undertaken to determine whether an in vivo/in vitro correlation can be established for bovine sulfamethazine oral boluses and to acquire insight into the magnitude of changes in in vitro product performance that can occur before corresponding changes are seen in in vivo blood level profiles. Based upon the results of this investigation, it is concluded that marked changes in in vitro sulfamethazine bolus performance can be tolerated before resulting in altered in vivo blood level profiles. However, the data also suggest that rumenal absorption may occur for some compounds. Therefore the degree to which variation in product in vitro dissolution profiles can be tolerated may be compound specific.
authors.affiliation: FDA Center for Veterinary Medicine, Office of New Animal Drug Evaluation, Rockville, MD, USA. marilyn.martinez@fda.hhs.gov
authors.forename: M N
authors.initials: MN
authors.lastname: Martinez
authors.forename: J C
authors.initials: JC
authors.lastname: Kawalek
authors.forename: K D
authors.initials: KD
authors.lastname: Howard
authors.forename: J L
authors.initials: JL
authors.lastname: Ward
authors.forename: P
authors.initials: P
authors.lastname: Marroum
authors.forename: W
authors.initials: W
authors.lastname: Marnane
authors.forename: D
authors.initials: D
authors.lastname: Bensley
authors.forename: F R
authors.initials: FR
authors.lastname: Pelsor
authors.forename: S
authors.initials: S
authors.lastname: Hoag
authors.forename: A S
authors.initials: AS
authors.lastname: Tatavarti
authors.forename: L
authors.initials: L
authors.lastname: Xie
authors.forename: R
authors.initials: R
authors.lastname: Fahmy
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002417:Cattle / Q000378:metabolism*; D002626:Chemistry, Pharmaceutical; D012995:Solubility; D013418:Sulfamethazine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D000890:Anti-Infective Agents; D013418:Sulfamethazine