Subject(s)
Estrogen Antagonists/pharmacology , Pyrrolidines/pharmacology , Receptors, Estrogen/agonists , Receptors, Estrogen/antagonists & inhibitors , Tetrahydronaphthalenes/pharmacology , Administration, Oral , Animals , Biological Availability , Bone Density/drug effects , Breast Neoplasms/pathology , Cell Division/drug effects , Cholesterol/blood , Estrogen Antagonists/administration & dosage , Estrogen Antagonists/metabolism , Estrogen Antagonists/pharmacokinetics , Ethinyl Estradiol/metabolism , Female , Humans , Hypolipidemic Agents/metabolism , Hypolipidemic Agents/pharmacology , Neoplasms, Hormone-Dependent/pathology , Organ Size/drug effects , Ovariectomy , Pyrrolidines/administration & dosage , Pyrrolidines/metabolism , Pyrrolidines/pharmacokinetics , Rats , Tetrahydronaphthalenes/administration & dosage , Tetrahydronaphthalenes/metabolism , Tetrahydronaphthalenes/pharmacokinetics , Tumor Cells, Cultured , Uterus/drug effectsABSTRACT
The plasma pharmacokinetics, lung tissue to plasma concentration ratios, and depletion profiles in edible tissue (liver, muscle, kidney, fat and injection site) for a single subcutaneous dose of a novel macrolide antibiotic, CP-163505 (20-[3-dimethylaminopropyl(L-alanyl)amino]-20-deoxo-repromicin), were investigated in crossbred beef cattle. Mean peak plasma concentration of 2.5 +/- 0.4 micrograms/mL, occurring at 0.5 h, was found for CP-163505 following a 5 mg/kg dose (n = 5). The pharmacokinetic profile consisted of a distribution phase, followed by an extended terminal elimination phase (t1/2 of 19 h). The disposition of CP-163505 was characterized by distribution from the plasma into the tissue resulting in lung to plasma ratios of 103 and 87 at 72 h following a single 5 or 10 mg/kg dose, respectively. The depletion of CP-163505 from edible tissues was determined following administration of tritiated CP-163505 at a dose of 10 mg/kg. On day 42, the liver contained the highest mean concentration of total tritium residues, 5.9 +/- 3.4 micrograms/g. CP-163505 was determined to be a significant component of the total residues in liver with 72% on day 3 and 50% on day 42. Three metabolites of CP-163505 were identified by liquid chromatography with mass spectrometry (LC/MS/MS) in liver samples: loss of alanine, formation of an hydroxyl derivative, and sulfate addition to the lactone ring.
Subject(s)
Anti-Bacterial Agents/pharmacokinetics , Drug Residues/analysis , Macrolides , Administration, Oral , Animals , Anti-Bacterial Agents/administration & dosage , Area Under Curve , Cattle , Chromatography, Liquid , Kidney/metabolism , Liver/metabolism , Lung/metabolism , Mass Spectrometry , Muscles/metabolism , Reproducibility of ResultsABSTRACT
We have described the case of a 46-year-old man with disseminated Pneumocystis carinii infection associated with cytomegalovirus pneumonitis. Because CMV causes endothelial damage in the lungs, we suggest that CMV pneumonitis is a risk factor for dissemination of P carinii infection beyond the lungs.
