The pharmacokinetics of ranitidine in patients with chronic duodenal ulceration and in patients with chronic renal failure

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dc.contributor.advisorFolb, Peter Ien_ZA
dc.contributor.authorMcFadyen, Margaret Lynnen_ZA
dc.date.accessioned2018-02-12T08:47:04Z
dc.date.available2018-02-12T08:47:04Z
dc.date.issued1981en_ZA
dc.description.abstractThe 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.en_ZA
dc.identifier.apacitationMcFadyen, M. L. (1981). <i>The pharmacokinetics of ranitidine in patients with chronic duodenal ulceration and in patients with chronic renal failure</i>. (Thesis). University of Cape Town ,Faculty of Health Sciences ,Division of Clinical Pharmacology. Retrieved from http://hdl.handle.net/11427/27517en_ZA
dc.identifier.chicagocitationMcFadyen, Margaret Lynn. <i>"The pharmacokinetics of ranitidine in patients with chronic duodenal ulceration and in patients with chronic renal failure."</i> Thesis., University of Cape Town ,Faculty of Health Sciences ,Division of Clinical Pharmacology, 1981. http://hdl.handle.net/11427/27517en_ZA
dc.identifier.citationMcFadyen, M. 1981. The pharmacokinetics of ranitidine in patients with chronic duodenal ulceration and in patients with chronic renal failure. University of Cape Town.en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - McFadyen, Margaret Lynn AB - 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. DA - 1981 DB - OpenUCT DP - University of Cape Town LK - https://open.uct.ac.za PB - University of Cape Town PY - 1981 T1 - The pharmacokinetics of ranitidine in patients with chronic duodenal ulceration and in patients with chronic renal failure TI - The pharmacokinetics of ranitidine in patients with chronic duodenal ulceration and in patients with chronic renal failure UR - http://hdl.handle.net/11427/27517 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/27517
dc.identifier.vancouvercitationMcFadyen ML. The pharmacokinetics of ranitidine in patients with chronic duodenal ulceration and in patients with chronic renal failure. [Thesis]. University of Cape Town ,Faculty of Health Sciences ,Division of Clinical Pharmacology, 1981 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/27517en_ZA
dc.language.isoengen_ZA
dc.publisher.departmentDivision of Clinical Pharmacologyen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.subject.otherDrug evaluationen_ZA
dc.subject.otherDrug Therapyen_ZA
dc.subject.otherKidney failure, Chronic - Drug therapyen_ZA
dc.subject.otherDuodenal diseasesen_ZA
dc.titleThe pharmacokinetics of ranitidine in patients with chronic duodenal ulceration and in patients with chronic renal failureen_ZA
dc.typeMaster Thesis
dc.type.qualificationlevelMasters
dc.type.qualificationnameMSc (Med)en_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceThesisen_ZA
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