Background:
Amprenavir (APV) and delavirdine (DLV) are both
primarily metabolized by cytochrome P450 (CYP) 3A4. The pill burden when
treating with APV is considerable (16 large pills). A regimen that could reduce
the APV pill burden without reducing antiretroviral effect would be desirable.
DLV might be an inhibitor of APV metabolism and thereby reducing the pill
burden. Data on steady-state concentrations of both drugs when given in a
combination are not available. The purpose of this study was to evaluate the
safety and pharmacokinetic interaction
between APV and DLV after multiple dose
administration in healthy volunteers.
Methods:
This was a prospective, open label, randomised, controlled study with 18
healthy male volunteers. They received either APV or DLV for 10 days and then a
combination of APV and DLV for another 10 days, with pharmacokinetic evaluation
on days 10 and 20. Results were compared with the Wilcoxon signed rank sum
test.
Results:
|
Group 1 (n = 9)
Dose
|
APV C12h (ng/mL)
Median (range)
|
APV AUC(0-12h) (ng/mL · h)
Median (range)
|
|
APV 600 mg BID
|
112 (53-287)
|
8737 (5829-17538)
|
|
APV + DLV 600 mg BID
|
252 (76-604)
|
20059 (11391-34143)
|
|
|
(p = 0.0039)
|
(p = 0.0039)
|
|
Group 2 (n = 9)
Dose
|
DLV C12h (ng/mL)
Median (range)
|
DLV AUC(0-12h) (ng/mL · h)
Median (range)
|
|
DLV 600 mg BID
|
7916 (1721-11562)
|
160609 (60884-223183)
|
|
DLV + APV 600 mg BID
|
933 (516-2547)
|
62715 (40307-87298)
|
|
|
(p = 0.0039)
|
(p = 0.0078)
|
Conclusions:
There is clinically significant interaction between APV and
DLV. A favourable increase in APV C12h but a dramatic decrease in
DLV C12h is seen. The regimen, APV 600 mg BID and DLV 600 mg BID, is
not recommended. Ongoing studies will elucidate whether other combinations are
suitable for clinical use.
