Thesis--Odense. / Summary in Danish. Includes bibliographical references (p. 136-[147]) and index.

Thesis--Odense. / Summary in Danish. Includes index. Bibliography: p. 136-[147]

The pharmacokinetics of orally administered ranitidine were studied in 10 patients with endoscopically proved duodenal ulceration after a single 150 mg dose and after 4 weeks 1 ranitidine treatment (150 mg twice daily), at which time there was endoscopic evidence of complete ulcer healing. After a single dose the median elimination half-life was 135 minutes and the median area under the curve (AUC) was l 844 ng/ml.hr. Although the maximum concentration after a single dose (Cmax = 365 ng/ml) was significantly different from that after continuous treatment (Cmax = 562 ng/ml) (p <0,05) there was no significant difference between the minimum concentrations at 12 hours post-dosing (Cmin = 35 ng/ml and 30 ng/ml respectively) and the median half-lives were identical. No accumulation of ranitidine occurred in these patients after 4 weeks' chronic ranitidine treatment. Five patients received 20 mg ranitidine intravenously. The apparent volume of distribution of the central compartment ranged from 10,5 to 28,4 1 while the elimination rate constant β range from 0,34 to 0,78 h⁻¹ with the t½ ranging from 53 to 122 minutes. The mean oral bioavailability was 51%. The pharmacokinetics of ranitidine were studied in a further 7 patients with chronic duodenal ulceration who showed endoscopic evidence of unhealed ulcers after at least 8 weeks' treatment with ranitidine. There were no significant differences in any of the pharmacokinetic parameters when these patients were compared with the 10 responders above after multiple-dosage except that the disposition rate constant was smaller in non-responders (0,24 h⁻¹ compared with 0,31 h⁻¹, p <0,002). Two patients did, however, have very low plasma concentrations with above average basal and maximal acid output which may have contributed to the lack of response to ranitidine treatment. Single- and multiple-dose pharmacokinetic studies of oral ranitidine were carried out in 6 patients with chronic renal failure (RF) (creatinine clearance <25 ml/min) and compared with those obtained for the 10 patients with chronic duodenal ulceration with normal renal function (creatinine clearance >65 ml/min). There appeared to be no significant differences in absorption rate or amount absorbed but the median elimination rate constant was significantly reduced from 0,31 h⁻¹ in controls to 0,14 h⁻¹ in RF (p <0,002) resulting in a two-fold increase in t½ (312 minutes) after a single dose. Cmax did not differ significantly although Cmin and AUC were significantly larger in RF patients (both p <0,002). It is suggested that the dosage of ranitidine be reduced from 150 mg to 75 mg twice daily in severe renal failure although it was not possible to relate half-life, elimination rate constant or AUC directly to creatinine clearance.