Abstract：
:Solid organ transplantation in HIV-infected individuals requires concomitant use of immunosuppressants and antiretrovirals that may cause significant drug interactions. Here we report on a peculiar pharmacokinetic interaction between tacrolimus and protease inhibitors (PIs) which occurred in four HIV-infected liver transplant patients who had to shift PI therapy from nelfinavir to fosamprenavir as a consequence of regulatory restrictions. After the switch, tacrolimus trough blood concentrations significantly dropped in all patients (mean +/- SD 6.9 +/- 2.6 versus 3.2 +/- 2.0 ng/ml before and after the switch, respectively; P=0.01), so that a marked dosage increase was needed (0.29 +/- 0.14 versus 0.88 +/- 0.48 mg/day, 1-3 days before and 3 weeks after the switch, respectively; P=0.046) to attain the desired target (8.7 +/- 2.3 ng/ml). Consistently, marked changes of the concentration/dose ratio of tacrolimus were observed in all cases (27.2 +/- 9.7 ng/ml per mg/kg/day versus 9.7 +/- 4.0 ng/ml per mg/kg/day before and after the switch, respectively; P<0.001). Our findings suggest that fosamprenavir may be less potent than nelfinavir in inhibiting tacrolimus clearance and support the need for higher tacrolimus dosage to avoid insufficient immunosuppression in HIV-infected liver transplant patients when switching from nelfinavir to fosamprenavir or even when directly starting antiretroviral therapy with fosamprenavir.
journal_name
Antivir Therjournal_title
Antiviral therapyauthors
Pea F,Tavio M,Pavan F,Londero A,Bresadola V,Adani GL,Furlanut M,Viale Psubject
Has Abstractpub_date
2008-01-01 00:00:00pages
739-42issue
5eissn
1359-6535issn
2040-2058journal_volume
13pub_type
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