. Author manuscript; available in PMC: 2021 Feb 1.

Published in final edited form as: Clin Pharmacol Ther. 2019 Oct 20;107(2):462–470. doi: 10.1002/cpt.1629

Table 2.

Multivariable mixed effects model for tacrolimus CDR

Variable	Percent Change in CDR^a
Post-operative day	−4.5 (−5.6, −3.4)
CYP3A5 Genotype^b
Poor metabolizers	ref.
Intermediate metabolizers	−51.7 (−59.9, −41.7)
Extensive metabolizers	−60.7 (−72.8, −43.4)
CYP3A4*22 LoF Allele	14.7 (−7.4, 42.2)
PPARA^c	5.3 (−7.2, 16.4)
POR*28^d	−2.5 (−15.9, 9.4)
ABCB1 3435C>T^e	−1.6 (−14.8, 13.8)
Hematocrit (5 % increase)	10.0 (5.9, 14.4)
Weight (10 kg increase)	−8.3 (−11.7, −4.8)
Primary graft dysfunction^f	18.5 (1.6, 38.1)
Procedure type
Single lung	ref.
Bilateral lung	40.7 (23.4, 60.5)
Cystic fibrosis	−28.9 (−44.6, −8.6)
Azole antifungal exposure^g
None	ref.
Fluconazole	21.3 (7.6, 36.8)
Voriconazole	79.7 (65.1, 95.5)
Amiodarone exposure	18.6 (11.0, 26.7)

^a)

analysis based on log-transformed CDRs. Model coefficients were exponentiated to provide the percentage change in CDR for a one unit change in each covariate, unless otherwise specified. Increases in CDR signify decreases in tacrolimus clearance

^b)

Likelihood ratio test, p<0.0001 for a model with CYP3A5 genotype vs. without genotype. The effects of CPIC defined intermediate vs. extensive metabolizer status on the CDR were similar (p=0.273)

^c)

At least one variant allele (GA, GG)

^d)

At least one variant allele (CT, TT)

^e)

At least one variant allele (CT, TT)

^f)

Grade 3 primary graft dysfunction at 48 or 72 hours after transplantation

^g)

Likelihood ratio test, p<0.0001