Biopharmaceutical aspects of FK-506

Abstract

FK is a potent immunosuppressive agent. FK can be analyzed in biologic fluids by EIA. The oral absorption of FK is rapid but variable in dogs. After intramuscular administration, FK is slowly and continuously absorbed. FK is primarily eliminated by metabolism. Less than 1% of the administered dose is excreted in the bile or the urine. After chronic intramuscular administration FK inhibits drug metabolism. Monitoring of FK levels in plasma is essential for the proper interpretation of efficacy and toxicity studies.

Fig 1

Chemical structure of FK-506.

Fig 2

Standard curve of plasma FK concentration v optical density at 492 nm.

Fig 3

Plasma concentration of FK in a dog (no. 2) on day 8 aftar daily oral administration of 1 mg/kg of FK.

Fig 4

Plasma concentration of FK in a dog. (no. 3) on day 8 aftar daily oral administration of 1 mg/kg of FK.

Fig 5

Area under tha plasma FK concentration–-v-time curve after oral administration of 1, 2, and 4 mg/kg of FK.

Fig 6

Plasma concentration of FK in dog no. 10(Δ) and dog no. 11 (O) after a single intramuscular injection of 0.49 mg/kg of FK.