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Ovine Fetal-Placental Cocaine Pharmacokinetics During Continuous Cocaine Infusion

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Abstract

Objective

TO investigate fetal-placental cocaine clearance, and to determine the fetal catecholamine and cardiovascular responses to continuous intravenous cocaine infusion in fetal sheep.

Methods

Eleven pregnant ewes and their fetuses (121 ± 2 days’ gestation; term 150 days) were chronically instrumented. Fetuses received intravenous cocaine at 0.05, 0.1, or 0.2 mg/kg/minute. Fetal cardiovascular and hematologic measurements were made before and serially for 90 minutes after initiation of the cocaine infusion.

Results

Steady-state fetal plasma cocaine concentrations were observed by 15 minutes of infusion and averaged 136 ± 77, 318 ± 65, and 610 ± 36 ng/mL, respectively, at each dose. Fetal-placental cocaine clearance rate was independent of dose (331 ± 39 mL/kg/minute), indicating that it is a first-order pharmacokinetic process. Fetal plasma concentration of benzoylecgonine, a principle cocaine metabolite, increased throughout the study to approximately 25% above cocaine levels by 90 minutes. Tliere were significant increases in fetal heart rate (from 169 ± 11 to 242 ±36 beats per minute), mean blood pressure (from 53 ± 4 to 63 ± 5 mmHg), and systolic blood pressure (from 68 + 2 to 80 ± 5 mmHg), with a corresponding increase in catecholamine levels seen in the fetuses infused with 0.2 mg/kg/minute. These changes were not seen in the fetuses given lower doses of cocaine.

Conclusion

Fetal-placental clearance of cocaine is a rapid, first-order pharmacokinetic process. During prolonged cocaine exposure, plasma benzoylecgonine concentrations accumulate significantly. Significant catecholamine and cardiovascular changes are seen in fetal sheep with a continuous infusion of cocaine at 0.2 mg/kg/minute or greater. (J Soc Gynecol Invest 1996;3:185-90)

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Harbor-UCLA Perinatal Research Laboratories, Torrance, California, 90502, USA, 1124 West Carson St.. Building #RBI

    Thomas Downs MD, James Padbury MD, Leslie Blount BS, Kent Kashiwai BS & Kenneth Chan MD

Authors
  1. Thomas Downs MD
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  2. James Padbury MD
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  3. Leslie Blount BS
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  4. Kent Kashiwai BS
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  5. Kenneth Chan MD
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Additional information

Supported by a grant from the USFHS DA-07753 and a Perinatal Biology Training Grant HD-07013.

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Downs, T., Padbury, J., Blount, L. et al. Ovine Fetal-Placental Cocaine Pharmacokinetics During Continuous Cocaine Infusion. Reprod. Sci. 3, 185–190 (1996). https://doi.org/10.1177/107155769600300405

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  • DOI: https://doi.org/10.1177/107155769600300405

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