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A DBS assay was developed for tacrolimus and MPA. Tacrolimus venous concentrations could be adequately predicted from DBS. DBS analysis of MPA seemed to be a semiquantitative measurement at the most when compared with conventional plasma analysis, considering the high variability between observed and predicted concentrations. Next, home-based DBS sampling of tacrolimus for the purpose of therapeutic drug monitoring will be implemented into routine clinical care.

single centre propectively collected outcome results on an early steroid withdrawal, low dose tacrolimus based immunosuppression in low immunologic risk living donor kidney transplantation. Induction therapy consisted of either 2 doses of basiliximab given 4 days apart or 2 doses of daclizumab, 1 mg/kg body wt, given 2 weeks apart. I.v. methylprednisolone 500 mg/day was given for 3 days beginning on day 0. Oral prednisolone was administered at a dose of 30/day for 3 days, 20 mg/day for 3 days, 15 mg/day for 3 days, 10 mg/ day for 3 days and continued on 5.0 mg/day until day 30 post transplant. Tacrolimus was started at a dose of 0.2 mg/kg body wt the night before the transplant, tacrolimus dose was adjuested to maintain the trough level at 8-12 ug/L for the fi rst 3 months, 5-8 ug/L from 3-12 months and 4-6 ug/L onwards. Mycophenolate was given at a dose of 750 mg b.i.d. for the fi rst 3 months and reduced to 500 mg b.i.d. later. Protocol biopsy was performed at day 10 post transplant, all suspected acute rejection episodes were biopsied. The 1-year acute rejection rate, 1-, 5-and 10-years patient and graft survival rates were studied. A total of 210 patients, mean age; 55.3±12.1 years (range 8-78 years), males:female; 136:64 were studied. Diabetes mellitus was the cause of endstage renal disease in 60% of patients. Subclinical rejection was detected in 5% of patients on protocol biopsy but was not treated if there was no rise in serum creatinine. The 1-year biopsy-confi rmed acute rejection and steroid-resistant rejection rates were 10% and 2% respectively. The 1-, 5-, and 10-years death censored graft survival rates were 99%, 95% and 90% respectively. The 1-, 5-and 10-years patient survival rates were 100%, 92% and 85% respectively. De novo diabetes mellitus occurred in 7% of patients at 1-year. 5/210 patients developed malignancy, 4 were PTLDs. In conclusion, early steroid withdrawal, low dose tacrolimus and mycophenolate based immunosuppression with anti-IL2 receptor induction therapy is an effective immunosuppression regimen with minimal complications for living donor kidney transplantation.

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.

PurposeThe aim of this study was to develop a clinically applicable limited sampling strategy for ambulatory Caucasian kidney transplant patients to estimate area under the curve in a 24-h period (AUC0–24) of prolonged-release tacrolimus.MethodsTwenty six kidney recipients, at least 6 months after transplantation, receiving prolonged-release tacrolimus, were enrolled. In each patient, seven blood samples were collected during a period of 24 h by use of the validated dried blood spot method. Best subset selection multiple linear regression was performed to derive limited sampling strategy (LSS). The equations were constrained to include a maximum of three samples collected within 4 h after the intake to maintain clinical applicability. To assess the predictive performance of LSS, residuals for each patient were calculated based on models fitted to a dataset where that patient was omitted.ResultsThe prediction formula for the AUC0–24 using the time points 0, 2, and 4 h after ingestion (C0h-C2h-C4h) provided the highest correlation with the AUC0–24 (r2 = 0.95): AUC0–24 = 44.9 + 8.9 × C0h + 2.1 × C2h + 7.6 × C4h. Measures for bias and precision, i.e., median percentage prediction error (MPPE) and median absolute prediction error (MAPE), were 0.4 and 4.8 %, respectively. For the same patients, the correlation between C24h and AUC0–24 was worse (r2 = 0.77) while MPPE and MAPE were 6.2 and 7.2 %, respectively.ConclusionIn the outpatient department, a LSS using C0h-C2h-C4h can be used for reliable estimation of the AUC0–24 of prolonged-release tacrolimus.Electronic supplementary materialThe online version of this article (doi:10.1007/s00228-015-1863-6) contains supplementary material, which is available to authorized users.

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Raltegravir does not influence the pharmacokinetics of citalopram and desmethylcitalopram. Citalopram did not change the pharmacokinetics of raltegravir in a clinically meaningful way. The combination was well tolerated and can be administered without dose adjustments. ClinicalTrials.gov NCT01978782.