A pharmacokinetic analysis of diclofenac potassium soft-gelatin capsule in patients after bunionectomy.
The clinical utility of diclofenac potassium, a nonsteroidal anti-inflammatory drug, may be lessened by inconsistent gastrointestinal absorption. Diclofenac potassium liquid filled soft-gelatin capsule (DPSGC) is an investigational formulation that uses ProSorb dispersion technology to facilitate rapid and consistent gastrointestinal absorption. In this study, the pharmacokinetic (PK) properties of DPSGC are investigated and compared with a commercially available oral diclofenac potassium tablet in patients after primary unilateral first metatarsal bunionectomy. In an open-label, randomized study, 53 patients received ProSorb-D 12.5 mg (the liquid equivalent of DPSGC), DPSGC 25 mg, DPSGC 50 mg, or immediate-release diclofenac potassium 50-mg tablet administered every 8 hours for a 24-hour inpatient period followed by 7 days of outpatient dosing. Diclofenac steady-state PK was evaluated over an 8-hour sampling period 4 days after surgery. Delayed and/or multiple peaks in the diclofenac plasma concentration-time course profiles occurred more frequently with the commercially available oral diclofenac potassium 50-mg tablet than with the other DPSGC formulations. PK data for ProSorb-D 12.5-mg liquid, DPSGC 25 mg, DPSGC 50 mg, and diclofenac potassium 50-mg tablet revealed mean peak plasma concentrations (Cmax) of 302, 749, 1006, and 902 ng/mL, respectively, whereas area under the plasma concentration curve values were 316, 595, 1029, and 1166 ng-hour/mL, respectively. Mean times to Cmax (tmax) were 0.49, 0.63, 0.95, and 1.26 h, respectively. When compared with absorption characteristics of diclofenac potassium 50-mg tablet, DPSGC was more rapidly and consistently absorbed after bunionectomy. These characteristics should be advantageous when rapid pain relief is desired.
Kowalski
Mark
M
AAIPharma, Inc., Wilmington, NC, USA. mkowalski@viventia.com
Stoker
Douglas G
DG
Bon
Charles
C
Moore
Keith A
KA
Boesing
Stephen E
SE
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D001682:Biological Availability; D002214:Capsules; D004008:Diclofenac / Q000097:blood* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D005534:Foot Diseases / Q000601:surgery*; D005780:Gelatin; D006215:Hallux Valgus / Q000601:surgery*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013607:Tablets; D014034:Toes / Q000601:surgery; D055815:Young Adult
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002214:Capsules; D013607:Tablets; D004008:Diclofenac; D005780:Gelatin