The absorption profile of pregabalin in chronic pancreatitis.
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 μg/ml (95% CI 1.69-2.34), and area under the plasma concentration-time profile (area under the curve) was 18.2 μg*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.
Mech-Sense, Department of Gastroenterology, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark.
Anne E
AE
Olesen
Erik
E
Olofsen
Søren S
SS
Olesen
Camilla
C
Staahl
Trine
T
Andresen
Albert
A
Dahan
Asbjørn M
AM
Drewes
D000042:Absorption; D000293:Adolescent; D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009426:Netherlands; D050500:Pancreatitis, Chronic / Q000188:drug therapy* / Q000503:physiopathology; D000069583:Pregabalin; D055815:Young Adult; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid