TABLE 3.

Intracellular levels of TFV-DP during single-dose or prolonged TFV treatment^a

Dose and animal no.	TFV dose (mg/kg)	Plasma TFV AUC0-24 (μg·h/ml)	Intracellular TFV-DP concn (fmol/106 PBMC) 24 h after dosing	Ratio of [intracellular TFV-DP] at 24 h to [mean plasma TFV] during dosing intervalb
Chronic dose
29046	0.6	4.5	52	0.40
29276	0.4	13.5	107	0.57
30577	1.0	4.3	48	0.38
31122	2.8	6.0	75	0.43
32186	0.4	4.5	53	0.41
33088	9.1	15.3	319	0.72
33091	2.1	4.4	45	0.35
Single dose
35391	4	6.0	76	0.44
35410	4	4.1	29	0.32
35434	4	5.8	31	0.18
35942	4	4.2	24	0.19

^aTFV was administered subcutaneously. Chronically dosed animals were on stable TFV regimens (administered once daily) for at least 7 weeks when the 24-h pharmacokinetics study was performed (see Table 1); an exception was animal 29276, which was dosed three times per week. Blood collected at specific time points after dosing was also used to isolate PBMC in order to measure intracellular TFV-DP levels. AUC_0-24, AUC from 0 to 24 h.

^bThe ratio of the intracellular TFV-DP concentration (24 h after dosing) to the mean plasma TFV concentration was calculated by assuming an approximate cell volume of 0.2 pl per cell (e.g., 100 fmol/10⁶ PBMC means 500 nM); the mean plasma TFV concentration was calculated by dividing the AUC by the dose interval and converting it also to nanomolar concentrations in order to calculate the unitless ratio. The geometric mean of the ratios for chronically dosed animals (0.47) was significantly higher than that for single-dosed animals (0.27) (P = 0.027 by a two-tailed t test on log-transformed ratios).