Bioanalysis of the Bicycle toxin conjugate BT5528 and released monomethyl auristatin E via liquid chromatography-tandem mass spectrometry.

The Bicycle toxin conjugate BT5528 is a novel peptide therapeutic conjugated to the cytotoxic agent monomethyl auristatin E (MMAE). A bioanalytical assay was developed to quantify BT5528 and unconjugated MMAE in human plasma. BT5528 quantitation used a protein precipitation procedure followed by LC-MS/MS detection.

Phase I safety and pharmacokinetic trials of 1263W94, a novel oral anti-human cytomegalovirus agent, in healthy and human immunodeficiency virus-infected subjects.

1263W94 [maribavir; 5,6-dichloro-2-(isopropylamino)-1, beta-L-ribofuranosyl-1-H-benzimidazole], a novel benzimidazole compound, has been demonstrated to potently and selectively inhibit human cytomegalovirus replication in vitro and to have favorable safety profiles in animal species. Two phase I trials evaluated the safety and pharmacokinetics of escalating single doses of 1263W94 in 13 healthy subjects (dose, 50 to 1,600 mg) and 17 human immunodeficiency virus (HIV)-infected subjects (dose, 100 to 1,600 mg). No severe safety concerns were observed in the evaluation of adverse events, vital signs, electrocardiograms, and clinical laboratory tests following administration of a single dose of 1263W94.