[Plasma levels of cyclosporin 6 hours after its oral administration, T6: key to the surveillance of the treatment].
Clinical evolution and CsA monitoring of 65 transplanted patients (55 kidneys and 10 kidneys and pancreas) treated with CsA were analysed, retrospectively (45 patients) and prospectively (34 patients). The aim of the study was: To show that nephrotoxicity is not uncommon with low trough plasma levels of CsA, and to indicate the value of CsA pharmacokinetic studies in individual cases. To suggest that the T6 value of a CsA pharmacokinetic plasma curve (6 hours after oral drug administration) is a valid expression of a full pharmacokinetics study. To show the results in a prospective study utilizing the T6 as a monitoring tool and with dose adjustments disregarding concomitant serum creatinine levels, with the aim of maintaining a therapeutic T6 (range 150-250 ng/ml). Patients with permanent Therapeutic T6 during the follow-up period (without dose adjustments) showed a creatinine serum level of 144 +/- 6 mumol/l. Serum creatinine levels decreased when CsA dose adjustments were made related to the presence of Toxic (greater than 350 ng/ml) or under-therapeutic (less than 100 ng/ml) T6 (p less than 0.01). Kidney and pancreas patients showed a tendency to under-therapeutic T6 and required a dose of 14 +/- 0.7 mg/kg to maintain a therapeutic T6. The CsA dose of kidney grafted patients through the T6 therapeutic period was 7.03 +/- 0.5 mg/kg. During the T6 toxic period, kidney patients received 8.85 +/- 0.3 mg/kg of CsA (p less than 0.02). Kidneys and graft survival is 97.6% at 6 months follow up in the prospective study. Current serum creatinine of all patients is 180.2 +/- 8 mumol/l. No patient was switched to conventional treatment. T6 is more useful than trough plasma levels for CsA monitoring. Nephrotoxicity and CsA under-treatment can be avoided. This new monitoring tool may allow the utilization of lower doses of CsA and thus contribute to improved graft function at long term follow-up.
Cantarovich
F
F
Clinique Néphrologique, Hôpital Edouard Herriot, Lyon.
Bizzolon
C
C
Cantarovich
D
D
Lefrançois
N
N
Dubernard
J M
JM
Traeger
J
J
D000284:Administration, Oral; D000328:Adult; D003404:Creatinine / Q000097:blood; D003524:Cyclosporins / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood* / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D007668:Kidney / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012189:Retrospective Studies; D013997:Time Factors
D003524:Cyclosporins; D003404:Creatinine
Les taux plasmatiques de cyclosporine 6 heures après son administration orale, T6: clé de la surveillance du traitement.