1995
DOI: 10.1128/aac.39.12.2779
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Pharmacokinetics of lamivudine and BCH-189 in plasma and cerebrospinal fluid of nonhuman primates

Abstract: 2-Deoxy-3-thiacytidine is a dideoxycytidine analog with a sulfur in place of the 3 carbon of the ribose. There are two enantiomeric forms of the compound, both of which inhibit human immunodeficiency virus type 1 and 2 replication in vitro. However, the (؊) enantiomer (lamivudine) appears to be significantly less cytotoxic to uninfected lymphocytes than is the (؉) enantiomer. Lamivudine has entered initial clinical trials, and the present study was designed to describe the pharmacokinetic behavior of this comp… Show more

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Cited by 47 publications
(30 citation statements)
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“…Indeed, concentrations of other antiretroviral drugs within CSF have been shown to vary depending on where the sample is taken. Lamivudine has been shown to be 5-fold higher in CSF sampled from the lumbar region than in ventricular CSF from rhesus monkeys (11). Although there are no comparable data for efavirenz in the literature, these data exemplify the challenges associated with predicting brain tissue concentrations based on CSF concentrations.…”
mentioning
confidence: 63%
See 1 more Smart Citation
“…Indeed, concentrations of other antiretroviral drugs within CSF have been shown to vary depending on where the sample is taken. Lamivudine has been shown to be 5-fold higher in CSF sampled from the lumbar region than in ventricular CSF from rhesus monkeys (11). Although there are no comparable data for efavirenz in the literature, these data exemplify the challenges associated with predicting brain tissue concentrations based on CSF concentrations.…”
mentioning
confidence: 63%
“…The appropriateness of CSF concentrations as a surrogate for brain concentrations is currently the subject of debate (10)(11)(12). It has been demonstrated in guinea pigs that brain tissue concentrations of nevirapine (NVP) not only differ from those in the CSF but also vary between brain regions (10).…”
mentioning
confidence: 99%
“…In addition, some compartments, including the CSF (12), genital secretions (21), and lymphoid tissue (29), have been shown to be poorly accessible to different antiretroviral drugs. In rhesus monkeys a dramatic difference in the levels and concentrationtime profiles of 2Ј-deoxy-3Ј-thiacytidine (3TC) between lumbar and ventricular CSF was observed (1). Therefore, the suboptimal therapeutic drug levels in the CNS and poor penetration of these drugs in various regions of the CNS may be more likely explanations for the independent evolution of drug-resistant variants in diverse areas of the CNS.…”
Section: Discussionmentioning
confidence: 99%
“…The systemic clearance (CL T ) value of 0.25 liter ⅐ h Ϫ1 ⅐ kg Ϫ1 for L-2Ј-Fd4C was comparatively low, considering the reported hepatic plasma and renal flow rates of 1.26 and 0.9 liter ⅐ h Ϫ1 ⅐ kg Ϫ1 , respectively, in monkeys (13). The total clearance of L-2Ј-Fd4C in rhesus monkeys was much lower than that of 3TC in rhesus monkeys (0.76 liter ⅐ h Ϫ1 ⅐ kg Ϫ1 ), with corresponding t 1/2 s in plasma of 5.02 and 1.40 h, respectively (1). CL R of L-2Ј-Fd4C in rhesus monkeys approached the glomerular filtration rate (0.16 compared to 0.2 liter ⅐ h Ϫ1 ⅐ kg Ϫ1 ) and suggests that elimination occurred by passive renal filtration.…”
Section: Discussionmentioning
confidence: 99%
“…The monkeys were given 33.3 mg of L-2Ј-Fd4C per kg of body weight i.v. (in 10 ml of PBS) so that comparisons could be made with results of previously reported studies (1,22,25,28). A washout period of at least 4 weeks was used between doses.…”
Section: Methodsmentioning
confidence: 99%