. Author manuscript; available in PMC: 2020 Aug 1.

Published in final edited form as: J Clin Pharmacol. 2018 Oct 29;59(3):309–325. doi: 10.1002/jcph.1325

Table 1.

Frequencies of Investigated Covariates

Demographic (97%)	>85%	Total body weight, age, sex
	10% to 25%	Race, height, body mass index, body surface area
	<10%	Lean body weight, donor age, ideal body weight, donor sex
Clinical/laboratory (94%)	> 54%	Hematocrit, ASAT, ALAT total bilirubin, serum creatinine
	28% to 50%	Serum albumin, alkaline phosphatase, hemoglobin, γ-glutamyltransferase, total protein
	10% to 20%	Blood/serum urea nitrogen, creatinine clearance, glomerular filtration rate, red blood cell
	< 10%	White blood cells, lactate dehydrogenase, C-reactive protein, INR, platelets, glucose, total cholesterol, high-density lipoprotein and low-density lipoprotein, triglycerides, factor V, hepatitis B virus, lutein dehydrogenase, B/P, E/P uric acid, creatinine kinase, bile drainage, 4β-hydroxycholesterol
Disease-related^a (84%)	> 70%	Postoperative day (POD)
	10% to 15%	Graft origin, graft/transplant size, total daily dose
	< 10%	Transplant size/body weight ratio, whole/split transplant, assay method, days of tacrolimus therapy, drug formulation, hot or cold ischemic time, diabetes mellitus, dialysis before transplant, preemptive transplant, cystic fibrosis, nephropathy, time of drug intake, biliary reconstructive procedure, Child-Pugh score, number of prior transplants, enrolling center, CMV serostatus, acute rejection episodes, body temperature, population (patient vs healthy volunteers), primary diagnosis
Cotreatment^a (59%)	46%	Immunosuppressant treatments: CST (prednisone, methylprednisolone), MMF, azathioprine, cyclosporine, basiliximab, daclizumab
Cotreatment^a (59%)	26%	Interactive drugs: β-blockers, calcium-channel blockers (diltiazem, verapamil, nifedipine, amlodipine, felodipine), ACEi, ARB, antibiotics (rifampicin, cotrimoxazole), anticonvulsants (phenytoin, phenobarbital), antifungal (fluconazole, amphotericin B), proton-pump inhibitor (pantoprazole, omeprazole), antidiabetic (sulfonylureas), diureties, anti-CMV drug, sodium bicarbonate, vitamin D analogues, oral contraceptives, oxybutynin, growth hormone
Genotypic^a (54%)	> 50%	CYP3A5 (rs776746)
	10% to 25%	CYP3A4 (rs35599367), ABCB1 (rs1128503, rs2032582, rs1045642)
	< 5%	CYP3A5 (rs10264272, rs41303343), CYP3A4 (rs2740574, rs2242480, rs12114000), ABCB1 (rs3213619, rs2229109), ABBC2 (rs717620, rs2273697, rs8187694, rs3740066), ABCG2 (rs2231142), PXR-hNR1I2 (rs3814055, rs1523127, rs2276706, rs1464603, rs6785049), POR28* (rs1057868), IL10 (rs1800896), SIM1 (rs3734354), SERPING1 (rs4926), APOA5 (rs3135506), GAN (rs2608555), ABCB1, CYP3A5 and CYP3A4 mRNA expression

ACEi indicates angiotensin-converting enzyme inhibitor; ALAT, alanine aminotransferase; ARB, angiotensin receptor blocker, ASAT, aspartate aminotransferase; B/P, blood to plasma concentration ratio; CMV, cytomegalovirus; CST, corticosteroids; E/P, erythrocyte to plasma concentration ratio; INR, international normalized ratio; MMF, mycophenolate mofetil.

Different frequencies between liver and renal transplant studies. Genotypic factors were investigated in 81% of renal transplant studies and in 21% of liver transplant studies. Disease-related factors were investigated in 77% of renal transplant studies and in 96% of liver transplant studies. Cotreatment was investigated as a covariate in 68% of renal transplant studies and in 57% of liver transplant studies.