Ranitidine kinetics and dynamics: I. Oral dose studies

Lebert, P A; MacLeod, Stuart; Mahon, W. A.; Soldin, Steven J.; Vandenberghe, Hilde

doi:10.1038/clpt.1981.200

Cited by 49 publications

(17 citation statements)

References 1 publication

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“…The t,~ in our subjects following intravenous dosing was 7.07 + 0.96 h which is a value that approximates that of 7.3 h observed by McFadyen et al [12] in near end-stage chronic renal failure patients and is similar to the value of 9.03 _+ 1.45 (SD) h demonstrated by Zech et al [25] in a like patient population. Like a number of other studies [1,4,8,14] we observed a higher ranitidine elimination t,~ following oral dosing (10.02 h). This phenomenon is not completely understood but may relate to prolonged absorption from the oral dosage form.…”

Section: Discussionsupporting

confidence: 63%

Ranitidine pharmacokinetics in continuous ambulatory peritoneal dialysis

Sica

Comstock

Harford

et al. 1987

Eur J Clin Pharmacol

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Ranitidine kinetics in renal failure were evaluated in six patients undergoing continuous ambulatory peritoneal dialysis (CAPD). On separate occasions each patient received either 50 mg intravenously (i.v.) or 150 mg orally of ranitidine HCl. Following i.v. administration, the plasma concentration vs time curve was best described by a two compartment model with firstorder elimination. The mean +/- SD distribution and elimination rate constants were 2.47 +/- 0.78 and 0.098 +/- 0.013 h, respectively. The area under the serum concentration vs time curve after the i.v. dose was 5979 +/- 2870 micrograms X h X l-1, resulting in a mean volume of distribution of 76.8 l and a total body clearance of 126 ml X min-1. Following oral administration the observed maximum plasma concentration was 904 +/- 483 micrograms X l-1 at 4.2 +/- 1.8 h, and the bioavailability was 69.7 +/- 35.6%. The peritoneal clearance of ranitidine was 3.2 +/- 0.7 and 2.6 +/- 0.6 ml X min-1 for the i.v. and oral groups, respectively. The amount of drug removed by dialysis was 561.2 +/- 336.2 micrograms for the i.v. and 1197.1 +/- 602.3 micrograms for the oral group. Four patients in the i.v. group had urine output during the study period with renal ranitidine clearance values of 9.9 +/- 9.9 ml X min-1. Two patients in the oral group had urine output and corresponding renal ranitidine clearance values of 5.1 and 20.1 ml X min-1. A dosage regimen for ranitidine is proposed based on ranitidine kinetics in patients undergoing CAPD.

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Section: Discussionsupporting

confidence: 63%

Ranitidine pharmacokinetics in continuous ambulatory peritoneal dialysis

Sica

Comstock

Harford

et al. 1987

Eur J Clin Pharmacol

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“…respec tively. Mignon et al [22] have demonstrated 50 and 80% reductions in acid output with ranitidine concentrations of 73 and 180 jj.g/1, respectively, which is consistent with other reports [23][24][25], Based on the mean bioavailability, elimination half-life, and volume of distribution in our patients, an approximate serum ranitidine concentration of 350 ¡.tg/i would result from a daily 150 mg oral dose if hemodialysis were not superimposed. For multiple intra venous dosing, 50 mg every 12-24 h should maintain serum concentrations consistently above 100 ug/1.…”

Section: Discussionsupporting

confidence: 79%

Ranitidine Bioavailability and Disposition Kinetics in Patients Undergoing Chronic Hemodialysis

Comstock¹,

Sica²,

Harford³

et al. 1989

Nephron

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The absorption and disposition of single-dose intravenous (i.v.) and oral ranitidine were evaluated in 6 patients undergoing chronic hemodialysis. Ranitidine was given as either 50 mg (0.16 mM) i.v. or 150 mg (0.48 mM) tablets 4 h prior to hemodialysis according to a randomized cross-over design with tests separated by 2 weeks. Following i.v. administration, the peak serum ranitidine concentration was 761 ± 207 µg/l (mean ± SD) and the observed peak after the oral dose was 833 ± 206 µg/l at 3.5 ± 1.2 h. To convert µg/l to µM/1, divide by 314. The terminal elimination rate constants for the i.v. and oral doses were 0.062 ± 0.013 and 0.058 ± 0.004 h^-1, respectively, with an apparent volume of distribution of 139.6 ± 35.3 liters and total body clearance 8.5 + 1.6 liters/h for the i.v. dose. Hemodialysis clearances during the i.v. and oral studies were 3.2 ± 0.9 and 3.1 ± 1.0 liters/h, respectively, and the mean amount removed by hemodialysis following i.v. administration was 3.9 ± 2.7 mg. The bioavailability of ranitidine was 54.3 ± 13.5%. Based on these single-dose data, a daily oral dose of 150 mg ranitidine in patients with end-stage renal disease should provide a mean ranitidine serum concentration of approximately 350 µg/l with less than 10% of body stores of ranitidine being lost during any dialysis session.

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“…The question of whether ranitidine maintenance dose should be reduced in this patient group is not easy to answer since overall only 58% of gastric aspirate samples had pH values which were compatible with effective suppression of acid secretion (i.e., pH > 4). This response rate occurred despite trough plasma ranitidine concentrations which were similar to (median = 0.11 mg [-1, range = 0.05-1.44 mg [71) those required to cause a 50% suppression of gastric acid secretion (range of means = 0.073-0.2 mg [-1) in healthy volunteers (Lebert et al, 1981b;Mignon et al, 1982;Holloway et al, 1984). Moreover, four of our patients failed to achieve significant elevation of gastric pH at any of the times at which measurements were made.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of ranitidine in critically ill patients.

Ilett¹,

Nation

Tjokrosetio³

et al. 1986

Brit J Clinical Pharma

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1 The plasma pharmacokinetics of ranitidine (50 mg i.v.) have been studied in 17 critically ill patients in an intensive care unit. Measurements of gastric aspirate pH were also made in 16 of these patients. Ranitidine therapy was part of the patients' normal drug regimen. 2 Ranitidine plasma concentration was measured by high performance liquid chromatography and appropriate polyexponential equations were fitted to concentration-time data to enable calculation of relevant pharmacokinetic parameters. Values of the volume of the initial dilution space (median = 89 ml kg-') and volume of distribution at steady state (median = 1.541 kg-') were about 60% of corresponding mean literature values for healthy controls. Plasma clearance (median = 4.22 ml min7l kg-1) and terminal half-life (median = 4.7 h) were about 2-3 fold less and 2-3 fold greater, respectively, than values for healthy controls. There was wide interpatient variation in all the pharmacokinetic parameters. Renal impairment was considered to be largely responsible for the low plasma clearance. 3 Gastric aspirate pH was measured at 0, 1 and 7 h after ranitidine administration and 58% of samples were found to be above pH 4. Four patients had gastric pH values which were consistently below pH 4 despite average trough plasma ranitidine concentrations equal to or greater than those required for a 50% suppression of gastric acid secretion in normal volunteers.

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Ranitidine kinetics and dynamics: I. Oral dose studies

Cited by 49 publications

References 1 publication

Ranitidine pharmacokinetics in continuous ambulatory peritoneal dialysis

Ranitidine pharmacokinetics in continuous ambulatory peritoneal dialysis

Ranitidine Bioavailability and Disposition Kinetics in Patients Undergoing Chronic Hemodialysis

Pharmacokinetics of ranitidine in critically ill patients.

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