Table 2.
Population parameter estimates of moxifloxacin pharmacokinetics
| Parameter description | Typical value (95% CI)a | Random variability (95% CI)a |
|---|---|---|
| Intrinsic CL during rifampicin-based TB treatment (L/h)b,c | 48.5 (44.1, 54.1) | BSV 14% (9.2, 19.4) |
| BOV 12.3% (0.1, 18.5) | ||
| Volume of central compartment (L)c | 126 (109.6, 134.5) | BSV 7% (0.1, 13.2) |
| Inter-compartmental CL (L/h)c | 2.04 (1.58, 4.71) | – |
| Volume of peripheral compartment (L)c | 30.5 (22.2, 54.4) | – |
| Pre-hepatic bioavailabilityd | 1 fixed | BOV 36.1% (26.9, 41.7) |
| Absorption lag time (h), priore | 0.55 (0.45, 0.74) | – |
| Absorption rate (Ka, 1/h), priore | 2.95 (1.21, 3.42) | BOV 104.5% (1.0, 121.0) |
| Hepatic plasma flow (L/h) | 50 fixed | |
| Moxifloxacin fraction unbound (%) | 50% fixed | |
| Change in intrinsic clearance while on single dose of moxifloxacin (%) | −29% (−37, −22) | |
| Change in pre-hepatic bioavailability while on single dose of moxifloxacin (%) | −23% (−33, −13) | |
| Change in intrinsic clearance while on efavirenz-based ART (%) | +42.4% (33, 58) | |
| Scaling factor for variability in bioavailability while on single dose of moxifloxacin (-fold)f | 0.62 (0.39, 0.89) | |
| Scaling factor for variability in bioavailability for unobserved doses (-fold)f | 2.5 (1.75,3.92) | |
| Proportional error (%) | 17.5 (12.3, 21.7) | |
| Additive error (mg/L) | 0.011 (0.005, 0.017) |
Obtained with a non-parametric bootstrap (n = 300).
Intrinsic CL of moxifloxacin when given at steady-state within rifampicin-based TB treatment and no efavirenz.
All CL and volume parameters have been allometrically scaled with FFM, and the typical values reported here refer to the typical patient, with FFM of 47 kg.
Pre-hepatic bioavailability is the fraction of the drug that is absorbed, crosses the gut wall unchanged, thus entering the portal vein and reaching the liver.
These parameters were estimated using a prior, as detailed in text.
These scaling factors modulate the size of the between-occasion variability in pre-hepatic bioavailability for the sections of data indicated (single dose and unobserved doses).