TABLE 2.
Summary of the models used to examine the influence of patient covariates on indinavir oral CL and oral V
| Hypothesisa | Modela | Parameter
|
ΔOFb | |||
|---|---|---|---|---|---|---|
| θa | θb | θc | θd | |||
| Demographic characteristics | ||||||
| Does BW influence CL? | θa · (1 + θb · BW) | 20.1 | 0.4 | −72.1 | ||
| V? | 73.0 | <0.1 | −0.0 | |||
| Does HT influence CL? | θa · (1 + θb · HT) | 19.3 | 0.3 | −23.9 | ||
| V? | 73.0 | <0.1 | −0.0 | |||
| Does age influence CL? | θa · (1 − θb · age) | 16.4 | 0.4 | −0.7 | ||
| V? | 73.0 | <0.1 | −0.0 | |||
| Does sex influence CL? (male: sex = 1) | θa · (1 + θb · sex) | 12.2 | 0.6 | −39.3 | ||
| V? | 73.1 | <0.1 | −0.0 | |||
| Does ethnicity influence CL? | ||||||
| Black (q = 0) vs not Black (q = 1) | θa · (1 − q) + θb · q | 16.5 | 14.7 | −0.7 | ||
| Caucasian (q = 0) vs non-Caucasian (q = 1) | 13.6 | 16.5 | −1.4 | |||
| Asian (q = 0) vs non-Asian (q = 1) | 11.6 | 16.3 | −0.7 | |||
| Hispanic (q = 0) vs non-Hispanic (q = 1) | 21.6 | 16.2 | −1.0 | |||
| Concomitant HIV medications on CL | ||||||
| PIs (ritonavir) (PIs = 1 if present) | CL = θa · (1 + θb · ritonavir) | 39.1 | −0.7 | −280.4 | ||
| RTIs (RTI = 1 if present) | ||||||
| Efavirenz | CL = θa · (1 + θb · RTI) | 16.3 | <0.1 | −0.1 | ||
| 3TC, AZT, stavudine, didanosine, abacavir | 16.2 | <0.1 | −0.0 | |||
| Other concomitant medications on CL | ||||||
| CYP3A4 inducersc (inducer = 1 if present) | CL = θa · (1 + θb · inducer) | 16.9 | 0.2 | −0.5 | ||
| CYP3A4 inhibitors (inhibitor = 1 if present) | CL = θa · (1 − θb · inhibitor) | 16.0 | <0.1 | −0.0 | ||
| Virological and immunologic factors on CL | ||||||
| Viral load (≤400 copies/mm3 = 1) | CL = θa · (1 + θb · viral load) | 15.7 | 0.1 | −2.6 | ||
| CD4 count (≥200 cells/mm3 = 1) | CL = θa · (1 + θb · CD4 count) | 15.7 | 0.1 | −2.6 | ||
| Association of significant covariates on CL | ||||||
| Ritonavir + BW | CL = θa · (1 + θb · ritonavir) · (1 + θc · BW) | 39.5 | −0.63 | 0.3 | −313.6 | |
| Ritonavir + BW + sex | CL = θa · (1 + θb · ritonavir) · (1 + θc · BW) · (1 + θd · sex) | 32.4 | −0.63 | 0.16 | 0.30 | −344.1 |
a
BW, body weight; HT, height; RTIs, reverse transcriptase inhibitors; AZT, zidovudine; 3TC, lamivudine. BW, height, and age are expressed as the relative deviation of individual measurements from the population mean.
b
ΔOF, difference in the NONMEM OF compared to the basic structural model, including no covariates; estimates of CL = 16.3 liters; V = 73 liters; Ka = 0.95 h−1; and F = 1.
c
Inducers included efavirenz.