Preclinical pharmacology of the HIV protease inhibitor, DG35 (NSC 654021) (Meeting abstract). NLM AIDSLINE Important note: Information in this article was accurate in 1995. The state of the art may have changed since the publication date.

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Preclinical pharmacology of the HIV protease inhibitor, DG35 (NSC 654021) (Meeting abstract).

Proc Annu Meet Am Assoc Cancer Res; 36:A2170 1995. Unique Identifier : AIDSLINE ICDB/95609945
Walker DL; Reid JM; Ames MM; Dept. of Oncology, Mayo Clinic, Rochester, MN 55905

Abstract: DG35 is a synthetic, HIV protease inhibitor under investigation by NCI as a potential anti-HIV agent. We have developed an HPLC assay for DG35 and characterized murine pharmacokinetics. DG35 was stable in organic solvents, pH7 and pH10 buffers, and biological fluids, but was susceptible to rapid hydrolysis under acidic conditions. Following iv administration to male CD2F1 mice, DG35 (10 mg/kg) plasma elimination was described by a 2-compartment open model: t1/2 alpha, t1/2 beta, Vss and ClTB values were 1.2 min, 12.7 min, 95.2 ml/kg and 92.4 ml/min/kg, respectively. Oral bioavailability and excretion in urine and feces were evaluated following iv and po administration of [3H]DG35. Apparent oral bioavailability (AUCpo/AUCiv) of total radioactivity was 36%, whereas bioavailability of DG35 was less than 3%. Urinary and fecal recoveries of total radioactivity were 8-18% and 64-86%, respectively. In those experiments, little parent drug was observed in urine (less than 1%) or feces (2-16%). The high excretion of total radioactivity, yet low recovery of parent drug in feces following oral administration, suggests that DG35 is well absorbed and extensively metabolized.
Keywords: Administration, Oral Animal Biological Availability Chromatography, High Pressure Liquid HIV Protease Inhibitors/ADMINISTRATION & DOSAGE/*PHARMACOKINETICS Injections, Intravenous Male Metabolic Clearance Rate Mice Mice, Inbred Strains Tissue Distribution ABSTRACTKWDadministration,oralanimalbiologicalavailabilitychromatography,highpressureliquidhivproteaseinhibitors/administration&dosage/KWDpharmacokineticsinjections,intravenousmalemetabolicclearanceratemicemice,inbredstrainstissuedistributionabstract
951230
M95C3234

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