Table 2.
Final Covariates Included in the Models
| Pharmacokinetic Parameter | Number of Studies With Significant Covariate(s) | Number of Significant Covariates | Covariate (Number of Studies Where It Was Retained as Significant) |
|---|---|---|---|
| CL(/F) | 62 | 29 | bCYP3A5*3 (n = 29), POD (n = 25),HCT (n = 18), BW (n = 16), ASAT (n = 7), Age (n = 7), tBIL (n = 6), ALB (n = 4), SCR (n = 4), DOSE (n = 4), immunosuppressant treatment (n = 4), interactive drugs use (n = 4), ALAT (n = 3),W/S (n = 3), LBW (n = 3),ALP (n = 2),GW(n = 2), tPROT (n = 2),GW/BW(n = 2), γGT (n = 2), dCYP3A4*22 (n = 1), ABCB1 mRNA (n = 1), ABCB1 haplotype (n = 2), ABCC2 haplotype (n = 1), FV (n = 1), DAY (n = 1),Population (n = 1), INR (n = 1),UREA (n = 1) |
| V(/F) | 29 | 13 | BW(n = 15), POD (n = 4), LBW (n = 2),HCT (n = 2), tPROT (n = 2),BSA (n = 1), ALAT (n = 1),Height (n = 1), E/P (n = 1), FORM (n = 2), immunosuppressant treatment (n = 1), BMI (n = 1), HB (n = 1) |
| aF | 8 | 10 | POD (n = 3), CYP3A5*3 (n = 3), Cotreatment (n = 2),DOSE (n = 2), BW (n = 1), tBIL (n = 1), FORM (n = 1), CF (n = 1), Age (n = 1), sex (n = 1) |
| Vp(/F) | 7 | 5 | BW(n = 3), LBW (n = 3), BSA (n = 1), RBC (n = 1),HCT (n = 1) |
| CLp(/F) | 6 | 3 | BW(n = 3), LBW (n = 3),HCT (n = 1) |
| ka | 4 | 3 | FORM (n = 2), Time of drug intake (n = 1), sub study (n = 1) |
| TLag | 3 | 3 | Diabetes mellitus (n = 1), POD (n = 1), substudy (n = 1) |
| Ktr | 2 | 2 | FORM (n = 1), CF (n = 1) |
ALAT indicates alanine aminotransferase; ALB, serum albumin; ALP, alkaline phosphatase; ASAT, aspartate aminotransferase; BMI, body mass index; BSA, body surface area; BW, total body weight;CF, cystic fibrosis;CL(/F), (apparent) central clearance; CLp(/F), (apparent) peripheral clearance;d-, donor (recipient otherwise); DAY, day of tacrolimus therapy; DOSE, total tacrolimus daily dose; E/P, erythrocyte to plasma ratio; F, bioavailability; FORM, tacrolimus formulation (immediate or prolonged-release); FV, factor V; γGT, γ-glutamyltransferase; GW, graft weight; HB, hemoglobin; HCT, hematocrit; INR, international normalized ratio; ka, absorption rate constant; ktr, transit compartment rate constant; LBW, lean body weight; POD, time posttransplant; Population, patient versus healthy volunteers RBC, red blood cells count; SCR, serum creatinine; tBIL, total bilirubin; TLag, absorption lag time; tPROT, total proteinemia; UREA, blood/serum urea nitrogen; V(/F), (apparent) central volume; Vp(/F), (apparent) peripheral volume; W/S, whole/split transplant.
F was estimated in 2 studies with intravenous data available, fixed to value from the literature 23% in 1 study. In 6 studies, covariates were reported on F relative to the value of 1.
CYP3A5*3 rs776746: recipient (n = 20 studies), donor (n = 2), both recipient and donor combined (n = 1) or not combined (n = 1), CYP3A5*3*6*7 genotypes (n = 1), CYP3A5*3 and CYP3A4*1G rs2242480 combined (n = 2), CY3A5*3 and CYP3A4*22 rs35599367 combined (n = 1), CYP3A5*3 and POR*28 rs1057868 combined (n = 1).