Pharmacokinetics of ethanol in pigtailed macaques: Intersubject variability and effect of subchronic administration

Kalhorn, Thomas F.; Bowden, Douglas M.; Slattery, John T.

doi:10.1016/0091-3057(86)90545-9

Cited by 9 publications

(5 citation statements)

References 20 publications

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“…Ethanol distributes rapidly throughout the body, based on our observations that plasma levels stabilize relatively quickly and follow first-order elimination kinetics within 7 min following the end of the slow intravenous infusion. This observation is consistent with the relatively stable plasma ethanol levels within 5--10 min following similar, slow infusion protocols for monkeys reported previously (Fuster et al 1982;Kalhorn et al 1986;Bennett and DePetrillo 2004). The plasma levels of ethanol attained after the 0.2 and 0.5 g/kg intravenous dose approximate plasma levels observed after intragastric doses of 1 and 2 g/kg, respectively (Ando et al 1987;Katner et al 2004).…”

Section: Discussionsupporting

confidence: 89%

The Acute Impact of Ethanol on Cognitive Performance in Rhesus Macaques

et al. 2010

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Decreased cognitive control over prepotent responses has been hypothesized to contribute to ethanol-induced behavioral disinhibition. However, the effects of ethanol on specific cognitive domains associated with decision making have not been extensively studied. We examined the impact of acute ethanol administration on cognitive performance of nonhuman primates. Studies were conducted using 0.2, 0.5, and 1 g/kg intravenous ethanol in rhesus macaques performing touch screen-based tasks examining stimulus discrimination, stimulus reversal, and stimulus response performance. The impact on attentional processing was also evaluated. Ethanol reduced the accuracy of reversal performance marginally at 0.2 g/kg and significantly at 0.5 g/kg. This effect was selective given an absence of impairment on the stimulus discrimination and stimulus response tasks at these doses. Performance on stimulus discrimination was impaired at 1.0 g/kg, which prevented determination of reversal performance. Analysis of post-error response times demonstrated that error processing was impaired at both 0.2 and 0.5 g/kg. Ethanol also increased the number of omissions and delayed responses on an attentional task, suggesting more frequent attentional lapses. These data demonstrate that cognitive function mediated by specific prefrontal cortical brain regions is particularly sensitive to ethanol and suggest specific cognitive mechanisms that may underlie harmful decisions made at low doses of ethanol.

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Section: Discussionsupporting

confidence: 89%

The Acute Impact of Ethanol on Cognitive Performance in Rhesus Macaques

et al. 2010

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“…The elimination rate we observed was congruent with previous reports. For example, Kalhorn and colleagues [12] reported a maximum ethanol metabolism rate of 0.199 g/kg/hour (0.0033 g/kg/minutes) following an i.v. bolus of 0.6 g/kg in pigtailed macaques, an estimate almost identical to that reported here.…”

Section: Discussionmentioning

confidence: 99%

“…One study investigated the V d of ethanol among various mammalian species, including six non‐human primates, to develop a common allometric equation relating kinetic parameters to a power of body weight [19]. Kalhorn and colleagues [12] studied the pharmacokinetics of ethanol in 11 pigtailed macaques ( Macaca nemestrina ) at intravenous doses selected to be comparable with quantities of ethanol voluntarily consumed by monkeys. However, in both of these studies data were from a small number of male subjects and could not address possible sex differences in V d or other kinetic parameters.…”

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confidence: 99%

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Sex differences in total body water in adolescent rhesus macaques estimated by ethanol dilution

Bennett¹,

DePetrillo²

2004

J of Medical Primatology

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Non-human primates are widely used in research, yet relatively few studies have addressed potential pharmacokinetic differences between males and females. The present study examined the relationship between total body water, sex, age, and weight in the rhesus macaque (Macaca mulatta). Ethanol-naïve, adolescent rhesus macaques (n = 119) were administered ethanol (males, 2.1 g/kg; females, 2.0 g/kg) intravenously, and blood samples for blood ethanol concentration obtained at 5, 10, and 60 minutes following the end of the infusion. Non-linear regression was used to compare and contrast a series of pharmacokinetic models examining the relationship between weight, sex, age, V(d) and zero-order elimination rate. V(d) (mean +/- SEM) for male rhesus was 0.771 +/- 0.008 l/kg and for females was 0.730 +/- 0.008 l/kg, different at P < 0.00001. There were no sex differences in the rate of zero-order ethanol elimination, estimated to be 0.0032 +/- 0.0004 g/kg/minute. The data reported here may be useful in designing and interpreting pharmacokinetic studies using rhesus monkeys.

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“…Pregnant female NHPs at the desired gestational stage received an intravenous injection of alcohol (2.15 g/kg) administered over a 2 minute period (time zero), then every hour for 6 hours a maintenance dose (0.2 g/kg) was administered to maintain the BAC in the range of 300-400 mg/dl (Kalhorn et al, 1986). This blood level was chosen because it approximates the BAC that a human fetus would be exposed to during a moderately heavy maternal binge drinking episode.…”

Section: Methodsmentioning

confidence: 99%

Alcohol-induced neuroapoptosis in the fetal macaque brain

Farber

Creeley

Olney

2010

Neurobiology of Disease

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The ability of brief exposure to alcohol to cause widespread neuroapoptosis in the developing rodent brain and subsequent long-term neurocognitive deficits has been proposed as a mechanism underlying the neurobehavioral deficits seen in fetal alcohol spectrum disorder (FASD). It is unknown whether brief exposure to alcohol causes apoptosis in the fetal primate brain. Pregnant fasicularis macaques at various stages of gestation (G105 to G155) were exposed to alcohol for 8 hours, then the fetuses were delivered by caesarian section and their brains perfused with fixative and evaluated for apoptosis. Compared to saline control brains, the ethanol-exposed brains displayed a pattern of neuroapoptosis that was widespread and similar to that caused by alcohol in infant rodent brain. The observed increase in apoptosis was on the order of 60-fold. We propose that the apoptogenic action of alcohol could explain many of the neuropathological changes and long-term neuropsychiatric disturbances associated with human FASD.

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Pharmacokinetics of ethanol in pigtailed macaques: Intersubject variability and effect of subchronic administration

Cited by 9 publications

References 20 publications

The Acute Impact of Ethanol on Cognitive Performance in Rhesus Macaques

The Acute Impact of Ethanol on Cognitive Performance in Rhesus Macaques

Sex differences in total body water in adolescent rhesus macaques estimated by ethanol dilution

Alcohol-induced neuroapoptosis in the fetal macaque brain

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