title: Investigation of human pharmacoscintigraphic behavior of two tablets and a capsule formulation of a high dose, poorly water soluble/highly permeable drug (efavirenz).
abstract: Human pharmacoscintigraphic behavior of two tablets and a capsule formulation of a high dose, poorly water soluble, highly permeable, micronized drug (efavirenz) was investigated. The tablets and capsule, prepared with samarium oxide and neutron activated to produce radioactive samarium-153, were evaluated for their in vivo disintegration and gastrointestinal (GI) transit in healthy subjects under fasted condition. Scintigraphic images were acquired to coincide with blood sampling times to assess the plasma concentration-time profile in relation to in vivo disintegration and GI transit. The mean gastric emptying times were approximately the same for all three formulations. Although in vivo dosage form disintegration was faster for Tablet A as compared to Tablet B and was similar between Tablet A and the capsule, Tablet A showed a slower rate and extent of drug absorption than Tablet B and the capsule. The results of this study eliminated the initial hypothesis that the difference in in vivo performance between the two tablet formulations is due to a different rate of in vivo disintegration and suggest that for this drug the in vivo dissolution rate of the drug from its disintegrated dosage form was a more important factor affecting the rate and extent of drug absorption.
authors.affiliation: Bristol-Myers Squibb Company, Biopharmaceutics R&D, New Brunswick, New Jersey 08903-0191, USA. zhihui.gao@bms.com
authors.forename: J Zh
authors.initials: JZh
authors.lastname: Gao
authors.forename: M A
authors.initials: MA
authors.lastname: Hussain
authors.forename: R
authors.initials: R
authors.lastname: Motheram
authors.forename: D A B
authors.initials: DA
authors.lastname: Gray
authors.forename: I H
authors.initials: IH
authors.lastname: Benedek
authors.forename: W D
authors.initials: WD
authors.lastname: Fiske
authors.forename: W J
authors.initials: WJ
authors.lastname: Doll
authors.forename: E
authors.initials: E
authors.lastname: Sandefer
authors.forename: R C
authors.initials: RC
authors.lastname: Page
authors.forename: G A
authors.initials: GA
authors.lastname: Digenis
mesh_terms: D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D048588:Benzoxazines / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D002214:Capsules; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D003521:Cyclopropanes; D015902:Gamma Cameras; D005746:Gastric Emptying; D041981:Gastrointestinal Tract / Q000000981:diagnostic imaging* / Q000378:metabolism; D005772:Gastrointestinal Transit; D006801:Humans; D008297:Male; D009501:Neutron Activation Analysis; D010539:Permeability; D011877:Radionuclide Imaging; D012995:Solubility; D013607:Tablets; D014867:Water / Q000737:chemistry
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D002214:Capsules; D003521:Cyclopropanes; D013607:Tablets; D014867:Water; C098320:efavirenz