The Absorption Profile of Pregabalin in Chronic Pancreatitis

Abstract

It was recently shown that pregabalin decreased pain associated with chronic pancreatitis. It is well known that pancreatitis patients suffer from fat malabsorption with accompanying diarrhoea because of loss of exocrine pancreatic enzyme production. This may lead to changes in the mucosal surface in the small intestine and possibly affect the absorption of pregabalin. The pharmacokinetics of pregabalin has never been investigated in patients suffering from chronic pancreatitis. The aim of this study was to develop a population pharmacokinetic model of pregabalin administered to patients with chronic pancreatitis. The pregabalin population pharmacokinetic analysis was conducted on data from fifteen patients with chronic pancreatitis. Each patient received 75 mg of pregabalin (oral capsule). Pregabalin concentrations were measured using a validated liquid chromatographic method. Data analysis was performed using non-linear mixed effects modelling methodology as implemented by NONMEM. A one-compartment model with first-order absorption and elimination adequately described pregabalin pharmacokinetics. Time to maximum observed plasma concentration (T max ) was 1.53 (95% CI 1.09-2.05). The maximum plasma concentration (C max ) was 1.98 lg/ml (95% CI 1.69-2.34), and area under the plasma concentration-time profile (area under the curve) was 18.2 lg*hr/ml (95% CI 14.7-26.3). Pregabalin is well absorbed in patients with chronic pancreatitis, and the pharmacokinetic profile of pregabalin is not extensively affected by chronic pancreatitis.

Quantitative Sensory Testing Predicts Pregabalin Efficacy in Painful Chronic Pancreatitis

“…However, as pregabalin reach a steady state plasma concentration after maximal 48 hours, the analgesic effect would theoretically be constant throughout the day when administered two times daily [25]. This is supported by a recent publication where the pharmacokinetic profile of pregabalin was reported in patient with CP and found to be comparable to that of healthy subjects [26]. Also, patients were asked to report the average pain score for the last 24 hours and not the pain score at the time of registration.…”

Comparison of oral absorption models for pregabalin: usefulness of transit compartment model

“…Pregabalin is rapidly absorbed in the fasting state, with peak plasma concentrations occurring within 1 h. Food reduces the absorption rate, resulting in lowered and delayed maximum plasma concentration without a clinically significant effect on the extent (bioavailability) 5. A few studies on the population PK of pregabalin have been conducted;6–8 these studies commonly employed a one-compartment model with first-order absorption and elimination only without mentioning any attempt to find a better model. However, in these studies, a common trend to underestimate pregabalin concentrations around the time of maximum plasma concentration (T max ) was observed, which suggests the possibility of an inappropriate choice of absorption model (first-order absorption).…”

Management of chronic pancreatitis: recent advances and future prospects

“… 47 , 48 Besides, it was also confirmed by a population pharmacokinetic model that pregabalin had a well-absorption profile in patients with CP. 49 However, a systematic review published in 2016 by Cochrane Library which only included the study of Olesen et al in 2011 suggested that the relevant evidence of pregabalin administration in CP patients was of low-to-moderate quality because of the short-term period of the trial and more adverse events compared with placebo group. 50 …”