Extemporaneous Compounding: A Possible Trigger Tool to Detect Potential Health Incidents.

BACKGROUND: Extemporaneous compounding (EC) involves the preparation of a therapeutic product for specific patient need. However, there is a potential relationship between this procedure and the occurrence of health incidents (HI). The use of trigger tools increases HI identification. OBJECTIVE: This study assessed the performance of EC as a trigger to detect potential health incidents arising from this procedure. METHODS: A one-month observational and cross-sectional study was performed in internal medicine ward and intensive care unit of medium-sized hospital. Data collection was carried out in 5 stages: all triggered patients with dysphagia or enteral feeding tube with prescription of EC were included; EC executed in prescribed standardized drugs was observed; the procedure was compared with the hospital guide and scientific literature; HI monitoring and their evaluation using WHO and NCC MERP algorithms; a search for pharmaceutical alternatives (PA) that would avoid the observed EC. RESULTS: 197 patients were recruited. Almost half of them were triggered by EC from 84 standardized drugs. 48 patients met the inclusion criteria. 28 adverse drug reactions, 01 therapeutic ineffectiveness, and 29 medication errors were identified. EC as a trigger tool showed a PPV value of 0.38. Only 24 drugs have PA available in the market, which could avoid one third of all observed EC. CONCLUSION: It was possible to detect potentially HI in one of two patients with enteral feeding tubes using EC as a trigger tool. The use of EC as a trigger tool contributes to identifying potential HI arising from drugs, which have not gotten pharmaceutical alternatives to be administered via enteral feeding tube.

Population pharmacokinetics of gabapentin in patients with neuropathic pain: Lack of effect of diabetes or glycaemic control.

AIMS: Gabapentin (GBP) is widely used to treat neuropathic pain, including diabetic neuropathic pain. Our objective was to evaluate the role of diabetes and glycaemic control on GBP population pharmacokinetics. METHODS: A clinical trial was conducted in patients with neuropathic pain (n = 29) due to type 2 diabetes (n = 19) or lumbar/cervical disc herniation (n = 10). All participants were treated with a single oral dose GBP. Blood was sampled up to 24 hours after GBP administration. Data were analysed with a population approach using the stochastic approximation expectation maximization algorithm. Weight, body mass index, sex, biomarkers of renal function and diabetes, and genotypes for the main genetic polymorphisms of SLC22A2 (rs316019) and SLC22A4 (rs1050152), the genes encoding the transporters for organic cations OCT2 and OCTN1, were tested as potential covariates. RESULTS: GBP drug disposition was described by a 1-compartment model with lag-time, first-order absorption and linear elimination. The total clearance was dependent on estimated glomerular filtration rate. Population estimates (between-subject variability in percentage) for lag time, first-order absorption rate, apparent volume of distribution and total clearance were 0.316 h (10.6%), 1.12 h-1 (10.7%), 140 L (7.7%) and 14.7 L/h (6.97%), respectively. No significant association was observed with hyperglycaemia, glycated haemoglobin, diabetes diagnosis, age, sex, weight, body mass index, SLC22A2 or SLC22A4 genotypes. CONCLUSION: This population pharmacokinetics model accurately estimated GBP concentrations in patients with neuropathic pain, using estimated glomerular filtrationrate as a covariate for total clearance. The distribution and excretion processes of GBP were not affected by hyperglycaemia or diabetes.

Cetirizine Reduces Gabapentin Plasma Concentrations and Effect: Role of Renal Drug Transporters for Organic Cations.

Gabapentin (GBP) is an organic cation mainly eliminated unchanged in urine, and active drug secretion has been suggested to contribute to its renal excretion. Our objective was to evaluate the potential drug-drug interaction between GBP and cetirizine (CTZ), an inhibitor of transporters for organic cations. An open-label, 2-period, crossover, nonrandomized clinical trial was conducted in patients with neuropathic pain to evaluate the effect of CTZ on GBP pharmacokinetics. Twelve participants were treated with a single dose of 300 mg GBP (treatment A) or with 20 mg/d of CTZ for 5 days and 300 mg GBP on the last day of CTZ treatment (treatment B). Blood sampling and pain intensity evaluation were performed up to 36 hours after GBP administration. The interaction of GBP and CTZ with transporters for organic cations was studied in human embryonic kidney (HEK) cells expressing the organic cation transporters (OCTs), multidrug and toxin extrusion proteins (MATEs), and OCTN1. CTZ treatment resulted in reduced area under the concentration-time curve and peak concentration compared with treatment A. In treatment B, the lower plasma concentrations of GBP resulted in reduced pain attenuation. GBP renal clearance was similar between treatments. GBP has low apparent affinity for OCT2 (concentration of an inhibitor where the response [or binding] is reduced by half [IC50 ] 237 µmol/L) and a high apparent affinity for hMATE1 (IC50 1.1 nmol/L), hMATE2-K (IC50 39 nmol/L), and hOCTN1 (IC50 2.1 nmol/L) in HEK cells. At therapeutic concentrations, CTZ interacts with hMATE1 and OCTN1. In summary, CTZ reduced the systemic exposure to GBP and its effect on neuropathic pain attenuation. However, CTZ × GBP interaction is not mediated by the renal transporters.