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The pharmacokinetics of ranitidine in patients with chronic duodenal ulceration and in patients with chronic renal failure
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 s...
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| Format: | Thesis |
| Language: | English |
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Division of Clinical Pharmacology
2018
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| _version_ | 1867613360782049280 |
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| access_status_str | Open Access |
| author | McFadyen, Margaret Lynn |
| author2 | Folb, Peter I |
| author_browse | Folb, Peter I McFadyen, Margaret Lynn |
| author_facet | Folb, Peter I McFadyen, Margaret Lynn |
| author_sort | McFadyen, Margaret Lynn |
| collection | Thesis |
| description | 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. |
| format | Thesis |
| id | oai:open.uct.ac.za:11427/27517 |
| institution | University of Cape Town (South Africa) |
| language | eng |
| last_indexed | 2026-06-10T12:34:55.155Z |
| license_str | Not specified — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UCTD — University of Cape Town Open Access Repository |
| publishDate | 2018 |
| publishDateRange | 2018 |
| publishDateSort | 2018 |
| publisher | Division of Clinical Pharmacology |
| publisherStr | Division of Clinical Pharmacology |
| record_format | dspace |
| source_str | UCTD — University of Cape Town Open Access Repository |
| spelling | oai:open.uct.ac.za:11427/27517 The pharmacokinetics of ranitidine in patients with chronic duodenal ulceration and in patients with chronic renal failure McFadyen, Margaret Lynn Folb, Peter I Drug evaluation Drug Therapy Kidney failure, Chronic - Drug therapy Duodenal diseases 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. 2018-02-12T08:47:04Z 2018-02-12T08:47:04Z 1981 Master Thesis Masters MSc (Med) http://hdl.handle.net/11427/27517 eng application/pdf Division of Clinical Pharmacology Faculty of Health Sciences University of Cape Town |
| spellingShingle | Drug evaluation Drug Therapy Kidney failure, Chronic - Drug therapy Duodenal diseases McFadyen, Margaret Lynn The pharmacokinetics of ranitidine in patients with chronic duodenal ulceration and in patients with chronic renal failure |
| thesis_degree_str | Master's |
| title | The pharmacokinetics of ranitidine in patients with chronic duodenal ulceration and in patients with chronic renal failure |
| title_full | The pharmacokinetics of ranitidine in patients with chronic duodenal ulceration and in patients with chronic renal failure |
| title_fullStr | The pharmacokinetics of ranitidine in patients with chronic duodenal ulceration and in patients with chronic renal failure |
| title_full_unstemmed | The pharmacokinetics of ranitidine in patients with chronic duodenal ulceration and in patients with chronic renal failure |
| title_short | The pharmacokinetics of ranitidine in patients with chronic duodenal ulceration and in patients with chronic renal failure |
| title_sort | pharmacokinetics of ranitidine in patients with chronic duodenal ulceration and in patients with chronic renal failure |
| topic | Drug evaluation Drug Therapy Kidney failure, Chronic - Drug therapy Duodenal diseases |
| url | http://hdl.handle.net/11427/27517 |
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