摘要:

Serum digoxin and metabolites were assayed in plasma and urine by HPLC in 10 dialysis‐dependent patients with end‐stage renal failure (group I) and in five patients with comparatively normal renal function (group II) after ingestion of 150 µCi3H‐digoxin‐12α. Thirteen patients were on maintenance digoxin therapy and were at steady state. Metabolites found regularly but usually in small amounts, were 3β‐digoxigenin and its mono‐ and bis‐digitoxosides, and 3‐keto and 3α(epi)‐digoxigenin. Quantitatively the most abundant metabolites were polar and averaged 26% (7 to 76) of the radioactivity in plasma 6 hr after drug, and 60% (11 to 88) for digoxin for all 15 patients. Neither values between group I and II for the polar metabolites nor digoxin differed significantly. The metabolites reacted with antibody to digoxin to varying degrees and may make up an important component of the serum digoxin concentration when determined by standard radioimmunoassay. In some patients, digoxin undergoes extensive biotransformation, mainly, we suggest by hydrolysis, oxidation, epimerization, and conjugation to polar end‐metabolites.Clinical Pharmacology and Therapeutics(1984)35,74–82

ISSN:0009-9236    

DOI:10.1038/clpt.1984.11

年代:1984

数据来源: WILEY

摘要:

Five‐day continuous intraperitoneal (ip) infusions of 5‐fluorouracil (FU) were injected into five patients as part of a phase 1 clinical pharmacology study. They received 20 courses through a totally implanted catheter/injection port system. Six courses are evaluable for kinetic parameters and all courses are evaluable for toxicity. In each course a 2 to 3 log FU concentration differential in favor of the peritoneal cavity was achieved and maintained. Steady‐state venous plasma FU concentrations averaged 0.34 µM, whereas steady‐state ip FU concentrations averaged 697 µM. Mean total body clearance (TBC) in these patients was 18.4 l/min and mean permeability‐area (PA) product for diffusion from the peritoneum was 13.7 ml/min. Mean TBC of 20 l/min with ip FU infusion was observed in one patient who also received a 24‐hr IV FU infusion for comparison. The TBC during the later infusion was 5.9 l/min. In this patient, calculations indicate 75% extraction of drug during the passage from the peritoneum to the systemic circulation, presumably representing in large part hepatic extraction of FU taken into the portal venous circulation. Ip constant infusion and bolus kinetics were compared in one patient. TBC for the ip bolus was 14.3 l/min, which was approximately half of the TBC of 29.5 l/min determined during the 5‐day constant ip infusion. Thus constant ip infusion of FU (1 gm/day) can provide an improved regional advantage over bolus ip FU because of an increased TBC. Toxicity was acceptable in all courses. Dose limiting toxicity was regional, namely moderate chemical peritonitis seen in two of the five patients on repeated courses. There was no myelosuppression, alopecia, nausea, or vomiting. There were no infectious complications. The only patient with measurable disease had an objective response in hepatic metastases from gastric cancer. The implanted device was well tolerated and facilitated peritoneal fluid sampling.Clinical Pharmacology and Therapeutics(1984)35,83–89; doi:10

ISSN:0009-9236    

DOI:10.1038/clpt.1984.12

年代:1984

数据来源: WILEY

摘要:

To measure their relative upper gastrointestinal irritant potential, either 5 mg amiloride and 50 mg hydrochlorothiazide (twice daily) or 24 mEq wax‐matrix potassium chloride (three times a day) were given to 30 normal subjects with no prior endoscopic abnormalities in the esophagus, stomach, or duodenum. All subjects received glycopyrrolate, 2 mg (3 times a day) to slow gastric emptying. Repeat endoscopy after 7 days of treatment with wax‐matrix potassium chloride revealed that 10 of 15 (67%) of the subjects developed one or more gradable upper gastrointestinal lesions (esophageal ulcer, gastric ulcer, eight cases of one or more mucosal erosions, and four cases of hyperemia or edema of the esophagus, stomach, or duodenum). Four subjects (27%) taking amiloride/hydrochlorothiazide developed either mild hyperemia or edema, but there were no erosions or ulcers in this group.Clinical Pharmacology and Therapeutics(1984)35,90–93; doi:10.1038/clpt.1

ISSN:0009-9236    

DOI:10.1038/clpt.1984.13

年代:1984

数据来源: WILEY

摘要:

Clinical Pharmacology and Therapeutics(1984)35,94–108; doi:10.1038/clpt.1984.

ISSN:0009-9236    

DOI:10.1038/clpt.1984.14

年代:1984

数据来源: WILEY

摘要:

Clinical Pharmacology and Therapeutics(1984)35,109–110; doi:10.1038/clpt.1984.

ISSN:0009-9236    

DOI:10.1038/clpt.1984.15

年代:1984

数据来源: WILEY

摘要:

Clinical Pharmacology and Therapeutics(1984)35,111–112; doi:10.1038/clpt.1984.

ISSN:0009-9236    

DOI:10.1038/clpt.1984.16

年代:1984

数据来源: WILEY

摘要:

Clinical Pharmacology and Therapeutics(1984)35,113–130; doi:10.1038/clpt.1984.

ISSN:0009-9236    

DOI:10.1038/clpt.1984.17

年代:1984

数据来源: WILEY