Pharmacokinetics of ranitidine in critically ill patients.

Abstract

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.

Prophylactic ranitidine treatment in critically ill children – a population pharmacokinetic study

“…The pharmacokinetic model developed in the present study revealed considerable IIV in the CL and V of ranitidine in critically ill children. This variability concurs with previously reported data obtained in critically ill adults and children in the paediatric intensive care unit . The estimated IIV (CV%) in the BASE model was 83.7 and 84.0% for CL and V , respectively (data not shown).…”

Pharmacodynamic modeling of the acid inhibitory effect of ranitidine in patients in an intensive care unit during prolonged dosing: Characterization of tolerance

“…Intravenous ranitidine is widely used as a prophylactic agent for stress ulcer–related bleeding in patients in an ICU 10 . Different intravenous regimens, repeated bolus injections, and primed continuous infusions have been used in patients in ICUs and tested in healthy volunteers 11 , 12 , 13 , 14 , 15 , 16 , 17 . However, the clinical responses and the conclusions drawn from these trials have often been contradictory 7 , 18 .…”

Clinical Pharmacology Studies in Critically Ill Children

“…Another study reported that ranitidine CL in critically ill children increased during the study period possibly due to concomitant administration of CYP inducers resulting in a reduced efficacy when recommended doses were administered [172]. All studies report that the ranitidine PK is highly variable in both critically ill adults and children and thus it is not possible to reliably compare the alterations [170–174]. …”