Table 1.

Pharmacokinetic parameters for rapamycin (0.1 mg/kg) following oral administration to 5 healthy dogs once (experiment 1) and, after a 2-week washout period, once daily for 5 consecutive days (experiment 2) as determined by compartmental NME analysis.

Parameter	Experiment 1		Experiment 2			Parameter characterizing the change in a given parameter on the last day (day 5) of rapamycin administration in experiment 2
	Mean estimate	IIV (%)	Mean estimate*	IIV (%)	IOV (%)	Parameter	P value
ka (h−1)	0.358	34.9	0.294	4.91	6.92	2.0	0.002
Cl/f (L•h/kg)	0.651	10.83	0.510	13.76	5.18	−0.519	0.003
V1/f (L/kg)	6.74	71.42	4.53	41.20	5.70	1.31	0.002
Q/f (L•h/kg)	1.02	10.33	1.12	38.75	—	—	—
V2/f (L/kg)	18.1	7.55	22.1	8.85	—	—	—

^*One dog was removed from the study on day 3 of experiment 2 because of an acutely ulcerated lipoma that required surgical removal; thus, the estimates for experiment 2 represent the mean for 4 dogs. IIV = Inter-individual variability. V₁/f = volume of the central compartment after oral administration, Q/f = Intercompartmental clearance of a drug after oral administration. V₂/f = Volume of the peripheral compartment after oral administration. — = Not calculated.