Table 9

Time-concentration profile of the drug and endogenous thiols in the PBMC of patient 3

Cyclophosphamide Course	Minutes	WR-1065	Mesna	Cys-SH	GSH
		μM
First amifostine infusion
Before amifostine infusion	0	<0.1	<0.1	273	3.9
End of amifostine infusion	17	131	<0.1	232	3.1
End of mesna infusion	36	136	26	234	4.4
End of cyclophosphamide ⁺ mesna infusions	67	50	26	268	3.6
Second amifostine infusion
End of amifostine infusion	18	136	?	234	2.5
17-min after amifostine infusion	35	115	?	187	2.4

Patient 3 received amifostine followed by mesna prior to cyclophosphamide, as follows: 0 to 0.25 h, amifostine 825 mg/m² i.v. over 15 min; 0.25 to 0.5 h, mesna 400 mg/m² i.v. over 15 min; 0.5 to 1.0 h, cyclophosphamide 2.1 g/m² plus mesna 400 mg/m² i.v. over 30 min; 1.0 to 4.0 h, mesna 400 mg/m² i.v. over 3 h; 3.0 to 3.25 h, amifostine 825 mg/m² i.v. over 15 min. Blood samples (1.0 ml each) were collected at 0, 0.25, 0.5, 1.0, 3.0, 3.25, 3.5, and 3.75 h. The PBMC were purified and analyzed as described under Materials and Methods. The yield (mean ± S.D.,n = 8) was 2.55 ± 0.27 × 10⁶cells/ml, mean cell volume 96 ± 2.7 fl, and total cell volume 0.22 ± 0.09 μl.