Comparative study of availability of prednisolone after intestinal infusion of prednisolone metasulfobenzoate and prednisone.
The role of intestinal absorption in the differential availability of prednisone (PN) and prednisolone metasulfobenzoate (PO-MS), which might account for clinical resistance to PO-MS, has been studied by an infusion technique. In a randomized cross-over design trial, a solution in isotonic saline of PN or PO-MS (115 mg.l-1 was infused at 5 ml.min-1 for 2 h, into a 25 cm segment of jejunum in 8 healthy fasting subjects. The intestinal content was partly collected and the flow rate at the end of the test segment was determined by using a water movement marker (PEG 4000). Plasma, intestinal and urine concentrations of PN and PO were determined by liquid chromatography. From the data on PO, the active molecule, the systemic availability of PO-MS was significantly smaller than of PN, with the respective mean AUCs being 1.71 and 3.60 mg.h-1. The difference was associated with smaller mean Cmax, 0.20 vs 0.64 mg.l-1, higher mean tmax, 2.94 vs 2.06 h and lower mean ka, 0.98 vs 2.18 l/h after PO-MS. No significant difference was found in the half-life or renal clearance of the formulations tested. The mean MRT was significantly increased after PO-MS, 6.82 vs 5.30 h. The observed difference probably reflected a difference in intestinal absorption. The mean absorption in the test segment of PO-MS was significantly smaller at 17.4 vs 85.5% for PN. The ester form may be a limiting factor in the intestinal absorption of PO.(ABSTRACT TRUNCATED AT 250 WORDS)
Rollin
C
C
Départment de Pharmacologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
Chosidow
O
O
Diquet
B
B
Dutreuil
C
C
Herson
S
S
Revuz
J
J
Delchier
J C
JC
D000328:Adult; D000704:Analysis of Variance; D001682:Biological Availability; D006801:Humans; D007322:Instillation, Drug; D007408:Intestinal Absorption; D007583:Jejunum / Q000378:metabolism; D008297:Male; D011239:Prednisolone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D011241:Prednisone / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012016:Reference Values
C013218:prednisolone 21-3-sulfobenzoate; D011239:Prednisolone; D011241:Prednisone