TABLE 2

Allometric equation coefficients, correlation coefficients, and predicted human pharmacokinetic parameters resulting from interspecies scaling of garenoxacin

Mean data (n = 3 to 4) from mice, rats, dogs, and monkeys were used for interspecies scaling. The mouse data were obtained from our previous report (Takahata et al, 1997). Correction factors tested were free fraction (f), maximum life span potential (MLP), brain weight (BW), UDP-glucuronyl transferase activity (UGT), and bile flow rate (Q).

Parameters
Allometric Coefficients
Allometric Exponents
Correlation Coefficients
Human Value
Predicted
Observed a
MRT (h) 3.56 0.303 0.826 13.5 — b
Vss (l) 1.16 0.942 0.986 73.0 71
Vss/f (l) 5.82 0.974 0.999 419 284 c
CLr (ml/min) 1.24 0.608 0.953 17.9 — b
CLr/f (ml/min) 6.22 0.639 0.931 103 — b
CLer (ml/min) 4.40 0.598 0.963 61 — b
CLer/f (ml/min) 22.1 0.629 0.904 350 — b
CL (ml/min) 5.84 0.607 0.991 84.1 86.1 d
CL · MLP (ml/min) 59.3 0.985 0.995 48.3 86.1 d
CL · BW (ml/min) 74.0 1.61 0.981 63.1 86.1 d
CL · UGT (ml/min) 22.3 0.913 0.979 390 86.1 d
CL · Q (ml/min) 0.0640 1.06 0.898 77.5 86.1 d
CL · UGT · Q (ml/min) 0.244 1.37 0.936 359 86.1 d
CL/f (ml/min) 29.3 0.638 0.933 483 344 c
CL/f · MLP (ml/min) 297 1.02 0.978 277 344 c
CL/f · BW (ml/min) 371 1.64 0.978 362 344 c
CL/f · UGT (ml/min) 112 0.944 0.931 2241 344 c
CL/f · Q (ml/min) 0.320 1.09 0.858 445 344 c
CL/f · UGT · Q (ml/min)
1.22
1.40
0.899
2065
344 c

  • ↵ a The human data were obtained from a presentation at the 41st ICCAC (Gajjar et al, 2001).

  • ↵ b The results were not obtained.

  • ↵ c Estimated from the free fraction in human serum of 0.25 (Bello et al., 2001).

  • ↵ d The CL was calculated from the value of the AUC (77.4 μg · h/ml) after intravenous 400-mg dose (Gajjar et al, 2001).