The clinical pharmacokinetics of two different preparations of intrarectal ketoprofen following spinal or local anesthesia for anal surgery.

Abstract

Two different preparations of commercially available suppositories containing Ketoprofen (KP) were administered to 49 patients immediately following anal surgery. The KP was prepared as either fatty suppositories (FS) or gelatin capsulated suppositories (GCS) and surgery was performed under either spinal (n = 37) or local anesthesia (n = 12). Similar results were observed in the kinetics of KP after both FS and GCS administration. The extent of bioavailability of the two dosage forms in the patient groups and control subjects (n = 10) were essentially equal. When the pharmacokinetic parameters of KP were compared between patient groups under spinal and local anesthesia, significant differences were found in the values of the peak level (C max), peak time (T max), and terminal phase half-life (t 1/2). The C max decreased by one-half, while the T max and t 1/2 increased twice and four times, respectively, in patient operated on under spinal anesthesia compared to those operated on under local anesthesia. The absorption rate constant (Ka) following spinal anesthesia was significantly less than that following local anesthesia or that of the healthy subjects (p less than 0.01). A "flip-flop" phenomena could be seen in the time profiles of plasma KP concentration following spinal anesthesia.