Drug utilization evaluation of parenteral proton pump inhibitors

Current evidence supports parenteral infusion of proton pump inhibitors (PPI) after endoscopic treatment of bleeding peptic ulcers and such treatment seems reasonable where there is active bleeding or visible vessel on endoscopy. Parenteral boluses of PPI can be used in patients nil by mouth who cannot tolerate oral therapy. We sought to examine the appropriateness of parenteral PPI use. Drug utilisation evaluation was performed on 94 patients admitted to a 500 bed metropolitan hospital. 39 patients received continuous parenteral infusion of omeprazole (8 mg/ h) over a mean of 60 ± 29 h. 55 patients had parenteral boluses (40 mg bd) of omeprazole over a mean of 5 ± 4 days. Indications for PPI infusion (n = 39) were: major haemorrhage requiring transfusion (23), minor haemorrhage (8), dyspepsia (4) and others (4). 31 of the 39 patients on PPI infusion had upper gastrointestinal (GI) endoscopy. PPI infusion was commenced prior to endoscopy in 26 (84%) patients. 13 patients (33%) had active bleeding or visible non bleeding vessels at endoscopy. Only 11 patients (28%) had endoscopically treated peptic ulcers. Indications for parenteral PPI boluses (n = 55) included patients nil by mouth unable to take maintenance PPI orally (21), minor haemorrhage (8), peptic ulcer prophylaxis in seriously unwell (6), major haemorrhage (4), dyspepsia (2), postoprative period following peptic ulcer surgery (2) and others (12). Endoscopy was performed in 10 patients (18%) with only 1 endoscopically treated peptic ulcer. Our data suggest significant inappropriate use of parenteral PPI, which may be used for minor GI bleeding and dyspepsia and are typically commenced prior to endoscopy. These findings can explain the costly hospital expenditure on PPI.

Bayesian population pharmacokinetic analysis of sirolimus

Objective: It is usual that data collected from routine clinical care is sparse and unable to support the more complex pharmacokinetic (PK) models that may have been reported in previous rich data studies. Informative priors may be a pre-requisite for model development. The aim of this study was to estimate the population PK parameters of sirolimus using a fully Bayesian approach with informative priors. Methods: Informative priors including prior mean and precision of the prior mean were elicited from previous published studies using a meta-analytic technique. Precision of between-subject variability was determined by simulations from a Wishart distribution using MATLAB (version 6.5). Concentration-time data of sirolimus retrospectively collected from kidney transplant patients were analysed using WinBUGS (version 1.3). The candidate models were either one- or two-compartment with first order absorption and first order elimination. Model discrimination was based on computation of the posterior odds supporting the model. Results: A total of 315 concentration-time points were obtained from 25 patients. Most data were clustered at trough concentrations with range of 1.6 to 77 hours post-dose. Using informative priors, either a one- or two-compartment model could be used to describe the data. When a one-compartment model was applied, information was gained from the data for the value of apparent clearance (CL/F = 18.5 L/h), and apparent volume of distribution (V/F = 1406 L) but no information was gained about the absorption rate constant (ka). When a two-compartment model was fitted to the data, the data were informative about CL/F, apparent inter-compartmental clearance, and apparent volume of distribution of the peripheral compartment (13.2 L/h, 20.8 L/h, and 579 L, respectively). The posterior distribution of the volume distribution of central compartment and ka were the same as priors. The posterior odds for the two-compartment model was 8.1, indicating the data supported the two-compartment model. Conclusion: The use of informative priors supported the choice of a more complex and informative model that would otherwise have not been supported by the sparse data.