Pharmacokinetics of rectal diclofenac and its hydroxy metabolites in man.
Diclofenac 100 mg suppository is well absorbed from the gastrointestinal tract of six human volunteers. Plasma concentrations of 4'-hydroxydiclofenac and diclofenac could be measured; the concentrations of the three other metabolites were below the detection limit of the HPLC analysis. The apparent half-lives of diclofenac and 4'-OH-diclofenac are, respectively 1.3 +/- 0.3 h and 4.3 +/- 1.0 h. When the t 1/2 values are derived from the renal excretion rate-time profiles, they are as follows: diclofenac 1.8 +/- 0.9 h, 3'-OH-, and 5-OH-diclofenac 2.3 +/- 1.0 h and 2.5 +/- 0.4 h, respectively, while those of 4'-OH- and 4',5-diOH-diclofenac are, respectively 3.6 +/- 0.5 h and 3.1 +/- 1.3 h. Diclofenac is excreted for 13.6 +/- 6.5%, its renal clearance (Clr) = 3.23 +/- 1.03 ml/min. The main metabolite excreted in the urine is 4'-OH-diclofenac (27.2 +/- 12% dose; Clr = 6.14 +/- 4.04 ml/min). The total body clearance of the parent drug and the apparent total body clearance of the main metabolite are similar, 28.0 +/- 11.9 l/h and 27.5 +/- 10.9 l/h.
Landsdorp
D
D
Department of Clinical Pharmacy, Sint Radboud University Hospital, Nijmegen, The Netherlands.
Vree
T B
TB
Janssen
T J
TJ
Guelen
P J
PJ
D000285:Administration, Rectal; D004008:Diclofenac / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D013997:Time Factors
D004008:Diclofenac