摘要:

We compared the pharmacokinetics of ticarcillin at a dose of 120 mg/kg in 11 patients with cystic fibrosis to 11 control subjects matched for age and sex. The mean elimination half‐life of ticarcillin in serum was 70.8 minutes in the control subjects and 53.1 minutes in the patients with cystic fibrosis. The total body clearance of ticarcillin was significantly higher in cystic fibrosis patients (65.6 ± 22.0 versus 46.2 ± 10.9 ml/min/m2in control subjects;p= 0.017). The nonrenal clearance of ticarcillin was also significantly higher in patients with cystic fibrosis (24.8 ± 11.1 versus 13.3 ± 6.0 ml/min/m2for the control group;p= 0.006). There was no significant difference in volume of distribution between the two groups. We concluded that the shorter elimination half‐life and the higher total body clearance of ticarcillin in patients with cystic fibrosis are a result of an increase in both renal and nonrenal elimination.Clinical Pharmacology and Therapeutics(1990)47,73–78; doi:10.1038/cl

ISSN:0009-9236    

DOI:10.1038/clpt.1990.11

年代:1990

数据来源: WILEY

摘要:

The effect of omeprazole treatment on diazepam plasma levels was studied in four slow and six rapid metabolizers of omeprazole. Single intravenous doses of diazepam (0.1 mg/kg) were administered after 1 week of oral treatment with omeprazole (20 mg) and placebo. This was a double‐blind crossover study with randomized placebo and omeprazole treatments. Blood was collected up to 120 hours after diazepam dosing (still during one‐daily omeprazole and placebo administration) for measurement of diazepam and its major metabolite desmethyldiazepam. The slow metabolizers of omeprazole also metabolized diazepam slowly, exhibiting only half the diazepam plasma clearance of the others. The mean clearance of diazepam was decreased 26% after omeprazole in the rapid metabolizers, whereas the slow group showed no apparent interaction. The mean plasma concentrations of desmethyldiazepam showed a more rapid formation in the rapid compared with the slow metabolizers, which is a logical consequence of the rate of diazepam metabolism.Clinical Pharmacology and Therapeutics(1990)47,79–85; doi:10.1038/clpt.1

ISSN:0009-9236    

DOI:10.1038/clpt.1990.12

年代:1990

数据来源: WILEY

摘要:

The influence of interferon‐induced fever on oral melphalan pharmacokinetics has been studied in 10 myeloma patients in a randomized crossover design. The melphalan dose (0.25 mg/kg) was given alone and 5 hours after the administration of human interferon alfa (7 × 106IU/m2), respectively. The plasma concentration of melphalan was determined by liquid chromatography with fluorometric detection after derivatization of melphalan withN‐acetylcysteine. The area under the plasma concentration‐time curve (AUC) was significantly lower (p= 0.02) when melphalan was given with interferon. There was a significant negative correlation (p= 0.008) between body temperature and dose normalized AUC, whereas no effect was noticed on the maximum plasma concentration (Cmax) and on the time to obtain Cmax. The rate of elimination showed a tendency (p= 0.06) to increase with increasing body temperature. It is suggested that the cytotoxicity of the drug is most probably enhanced because of the higher alkylating activity of the compound at elevated body temperatures.Clinical Pharmacology and Therapeutics(1990)47,86–90; doi:10.1038/clp

ISSN:0009-9236    

DOI:10.1038/clpt.1990.13

年代:1990

数据来源: WILEY

摘要:

Clinical Pharmacology and Therapeutics(1990)47,91–93; doi:10.1038/clpt.1990.

ISSN:0009-9236    

DOI:10.1038/clpt.1990.14

年代:1990

数据来源: WILEY

摘要:

Clinical Pharmacology and Therapeutics(1990)47,94–94; doi:10.1038/clpt.1990.

ISSN:0009-9236    

DOI:10.1038/clpt.1990.15

年代:1990

数据来源: WILEY

摘要:

Clinical Pharmacology and Therapeutics(1990)47,95–124; doi:10.1038/clpt.1990.

ISSN:0009-9236    

DOI:10.1038/clpt.1990.16

年代:1990

数据来源: WILEY