Pharmacokinetics of Nitrosoureas: Comparison of 1,3-Bis-(2-Chloroethyl)-1-Nitrosourea (Bcnu) and 1-(2-Chloroethyl)-3-Cyclohexyl-1-Nitrosourea (Ccnu) after Oral and Intravenous Administration to Rats
Restricted accessResearch articleFirst published online December, 1984
Pharmacokinetics of Nitrosoureas: Comparison of 1,3-Bis-(2-Chloroethyl)-1-Nitrosourea (Bcnu) and 1-(2-Chloroethyl)-3-Cyclohexyl-1-Nitrosourea (Ccnu) after Oral and Intravenous Administration to Rats
Differential pulse Polarographic assay of intact nitrosoureas revealed the lower bioavailability of CCNU (1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea) in stomach and liver after oral administration to rats in comparison to BCNU (1,3-bis-(2-chloroethyl)-1-nitrosourea); blood levels of CCNU were below the detection limit of the method (20 ng). After i.v. bolus the CCNU concentration in plasma fell faster than that of BCNU. The rate of CCNU decomposition during incubation with blood at 37 °C was 3 times lower than that of BCNU.
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References
1.
BartošekI., DanielS., SykoraS.: Differential pulse Polarographic determination of submicrogram quantities of carmustine and related compounds in biological samples. J. Pharm. Sci., 67: 1160–1163, 1978.
2.
ClineM.J., HaskellC.M.: Cancer Chemotherapy, 3rd ed., Saunders, Philadelphia, 1980.
3.
GibaldiM., PerrierD.: Pharmacokinetics, Marcel Dekker, New York, 1975.
4.
LessnerH.E., VoglerW.R.: Toxicity study of BCNU (NSC-409962) given orally. Cancer Chemother. Rep., 58: 407–411, 1974.
5.
LevinV.A., KabraP.: Effectiveness of the nitrosoureas as a function of their lipid solubility in the chemotherapy of experimental rat brain tumors. Cancer Chemother. Rep., 58: 787–792, 1974.
6.
LevinV.A., KabraP.A., Freeman-DoveM.A.: Relationship of 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU) and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) pharmacokinetics of uptake, distribution and tissue/plasma partitioning in rat organs and intracerebral tumors. Cancer Chemother. Rep., 1: 233–242, 1978.
7.
PanasciL.C., GreenD., NagourneyR., FoxP., ScheinP.S.: A structure-activity analysis of chemical and biological parameters of chloroethylnitrosoureas in mice. Cancer Res., 37: 2615–2618, 1977.
8.
RussoR.G., BartošekI., PiazzaE., SantiA.M., LibrettiA., GarattiniS.: Differential pulse Polarographic determination of pharmacokinetics of 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU) in patients with lung cancer. Cancer Treat. Rep., 65: 555–562, 1981.
9.
SpreaficoF., FilippeschiS., FalautanoP., EisenbrandG., FiebigH.H., HabsH., ZellerV., BergerM., SchmahlD., Van PuttenL.M., SminkT., CsanyiE., Somfai-RelleS.: EORTC studies with novel nitrosoureas. In: Nitrosoureas-Current Status and New Development, pp. 27–42, PrestaykoA.W., CrookeS.T., BakerL.H., CarterS.K., ScheinP.S. (Eds.), Academic Press, New York, 1981.
10.
ThompsonG.R., LarsonR.E.: A toxicologic comparison of the potency and activity of 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU) and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) in mice and rats. Toxicol. Appl. Pharmacol., 21: 405–413, 1972.
11.
WassermannT.H.: The nitrosoureas: an outline of clinical schedules and toxic effects. Cancer Treat. Rep., 60: 709–711, 1976.
