The results of this study provide evidence for safe conversion from Tacrolimus BID to QD with appropriate trough concentration monitoring.

The usefulness of dried blood spot (DBS) sampling for therapeutic drug monitoring of tacrolimus was investigated with renal transplant patients. There was no significant difference between the concentrations (ranging 3.33-53.9 mug/l) of 34 samples of 26 stable renal transplant outpatients, measured both after venous and DBS sampling. DBS sampling is easy to perform because concentrations with and without nurse assistance did not significantly differ. No significant difference was found between tacrolimus concentrations in 20 duplicate DBS samples before and after postal transport. DBS seems promising for routine patient monitoring.

No abstract

FK 506 was compared with cyclosporin in a randomised trial in good-risk cadaveric renal transplant recipients. The objective was to evaluate whether oral FK 506 dosing was viable and whether blood concentrations in the range 10-20 ng/ml would prove to be practical. Thirty-one adult patients were randomised to FK 506 and 16 to cyclosporin. Both groups received an identical regimen of azathioprine and corticosteroids. Serum creatinine concentrations decreased rapidly in both groups with mean values below 200 mumol/l within 2 weeks. One graft in the cyclosporin group was lost due to renal vein thrombosis. During the 6-week study period, 19.4% of patients on FK 506 and 31.3% on cyclosporin experienced acute rejection. One patient in each group experienced corticosteroid-resistant rejection that responded to anti-lymphocyte therapy. Infections were reported in 51.6% of the FK 506 group compared with 37.5% of the cyclosporin group. The spectrum of adverse events was similar in both groups. However, minor neurological disorders were more common in the FK 506 group (54.8% versus 6.3%) whereas hypertension was less common (48.8% versus 75.0%). The results indicate that oral FK 506 rapidly achieves therapeutic blood concentrations and is an effective immunosuppressant for the initial treatment of renal allograft recipients.

Summary This multicenter, open, phase IIIb study assessed short‐term efficacy, safety and dose adjustments in adult stable renal transplant recipients converted from tacrolimus twice‐daily (BID) to once‐daily (QD). Patients receiving unchanged tacrolimus BID for ≥12 weeks were enrolled, and after 6‐weeks, converted from tacrolimus BID to QD (morning dose) on a 1 : 1 (mg : mg) total daily dose basis, for a further 12 weeks. Primary endpoint: change in steady‐state creatinine clearance between treatment phases. Secondary endpoints: biopsy‐proven acute rejection (BPAR), patient and graft survival, safety. 128 patients enrolled (mean age 48.9 years; time post‐transplant 48.9 months); 91 evaluated for the primary endpoint. Mean total daily dose was 0.06 mg/kg (BID) and 0.07 mg/kg (QD); 79.1% required one/no dose changes post‐conversion to maintain recommended blood‐trough levels; average dose increase was small (0.6–0.7 mg/day) with more dose increases in patients on the lowest tacrolimus BID doses. Renal function remained stable and non‐inferiority of tacrolimus QD against tacrolimus BID was demonstrated. There were no BPAR episodes; patient and graft survival were 100%. Adverse events were few; none led to dose modifications/discontinuation. Tacrolimus BID to tacrolimus QD conversion is straightforward and does not compromise renal function in stable kidney transplant patients in the short term.