Clinical efficacy and pharmacokinetics of tacrolimus in children with steroid-resistant nephrotic syndrome.

BACKGROUND: Tacrolimus has gained acceptance in the management of steroid-resistant nephrotic syndrome (SRNS) in children. Due to limited data, therapeutic range is extrapolated from pediatric renal transplant recipients. This study was designed to assess therapeutic efficacy of tacrolimus in children with SRNS and its correlation with inter-dose area under concentration curve (AUC0-12 h) and trough concentration (C0).

METHODS: Pre dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3, 4, 8, and 12 h after drug administration blood samples were collected in 25 children who were on tacrolimus for a minimum of 3 months and AUC0-12 h was calculated.

RESULTS: There was an 80% (20/25) response rate with 64% (16/25) children achieving complete remission. Median C0 in remission was higher than in relapse group (2.95 ng/ml, versus 1.20 ng/ml, p = 0.005). Median AUC0-12 h in remission was higher compared to those in relapse group (79.75 versus 35.15 μg × h/l; p = 0.025). Maximum concentration after drug administration (Cmax) among the groups was not significantly different. There was a significant correlation between C0 and AUC0-12 h (r = 0.79); and Cmax and AUC0-12 h (r = 0.84). Five patients had a rise in serum creatinine, of which four were still proteinuric and had lower C0 and AUC0-12 h. No other adverse effect was noted.

CONCLUSIONS: Tacrolimus had beneficial clinical response in SRNS. Target C0 and AUC0-12 h level for treatment remission was higher than those in relapse in children with SRNS but was lower than required in transplant recipient.