Protein binding of glycopeptide antibiotics with diverse physical-chemical properties in mouse, rat, and human serum.

In previous studies of the pharmacokinetics and urinary excretion of nine glycopeptides with diverse isoelectric points (pI), as pI decreases, the total systemic and renal clearance, urinary recovery, and volume of distribution decrease, whereas the half-life increases. With glycopeptides of similar pI, clearance decreases and half-life increases with increasing lipophilicity. The present study examines the serum protein binding of these glycopeptide antibiotics in mouse, rat, and human serum and calculates the previously reported pharmacokinetic parameters for these drugs based on unbound concentration.

Pharmacokinetics of dopamine-2 agonists in rats and dogs.

The absorption, protein binding, blood-to-plasma ratio, renal excretion, and pharmacokinetics of the dopamine-2 agonists (D2-agonists) 4-(2-di-n-propylaminoethyl)-7-hydroxy-2-(3H)-indolone (1), N-(2'-hydroxy-5'-[N,N-di-n-propylaminoethylphenyl])methanesulfonamide (2), and 4-(2-di-n-propylaminoethyl)-2-(3H)-indolone (3) were examined in dogs and rats. On the basis of relative cumulative urinary recoveries of radiolabeled drug, all three compounds are well absorbed in rats and dogs. In dogs, the free fractions in plasma of unchanged 1, 2, and 3, determined by in vitro studies, were 74, 86, and 63%, respectively, and the protein binding was constant with increasing concentration.

Distribution in normal and inflammatory tissue of a new semisynthetic cephalosporin, SK&F 75073.

SK&F 75073 is a new cephalosporin with broad spectrum antibacterial activity. SK&F 75073-14C and cefazolin-35S were administered separately to groups of rats as a single intramuscular dose of 20 mg/kg. Tissues with highest drug levels 15 minutes following dose were as follows: (SK&F 75073/cefazolin levels), kidney - 86/70 microgram/g, liver - 33/22 microgram/g, lung - 29/17 microgram/g, heart - 23/10 microgram/g, adrenal - 13/7 microgram/g.