Therapeutic drug monitoring of tacrolimus in early stage after heart transplantation

Abstract Introduction Little is known about the pharmacokinetic (PK) profiles of tacrolimus (Tac) within the first week after heart transplantation (HT) in adults. Our objective was to investigate the PK profiles of Tac in early after HT. Methods Twenty-three adult HT patients received Tac as primary immunosuppression. Tac was administered orally at a starting dosage of 0.10 mg/kg/d. The Tac dosages were adjusted to a target range of 10 to 20 ng/mL during the first 1 month after HT. The PK profiles were analyzed immediately after the first dose (PK1; n = 14), at day 3 (PK2; n = 10), and at day 7 (PK3; n = 8) to assess the relationships between PK parameters and acute rejection rates. Results The correlation between Tac trough levels and Tac-AUCs were r = .95 PK1; r = .82, PK2; and r = .88, PK3. When AUC 0–12h was controlled in the range from 150 to 300 ng · h/mL (10 to 20 ng/mL trough levels), 17 of 18 patients (94.4%) did not show evidence of significant rejection (72.2% grade 0, 16.7% 1A, and 5.5% grade 1B). One patient displayed a grade 2 biopsy score (5.5%). Mean AUC 0–12h values of Tac were significantly lower among patients who experienced acute rejection than those who remained rejection-free (89 vs 217 ng · h/mL, P = .023). Conclusion The initial trough levels are good indicators of systemic exposure. To reduce the risk of rejection and renal toxicity, the trough levels should be controlled in range from 10 to 20 ng/mL in early stage after HT.