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Urinary Clearance of 11-Nor-9-Carboxy-Δ9-Tetrahydrocannabinol (THCCOOH): A Detailed Pharmacokinetic Analysis
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  • Cristina Sempio,
  • Marilyn Huestis,
  • Bruce Kaplan,
  • Jost Klawitter,
  • Uwe Christians,
  • Thomas Henthorn
Cristina Sempio
University of Colorado Denver School of Medicine
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Marilyn Huestis
National Institute on Drug Abuse
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Bruce Kaplan
University of Colorado Denver School of Medicine
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Jost Klawitter
University of Colorado Denver
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Uwe Christians
University of Colorado Denver School of Medicine
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Thomas Henthorn
University of Colorado Denver School of Medicine

Corresponding Author:[email protected]

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Abstract

Background. Urine is a common matrix for screening for cannabis use. Urine assays typically measure total THCCOOH concentrations after hydrolysis cleaves the glucuronide. Urine THCCOOH concentration is adjusted by urine creatinine concentration or specific gravity, to account for variable hydration states. Therefore, we performed a population pharmacokinetic analysis of the urinary THCCOOH excretion, urinary flow rate, and creatinine excretion rate data. Methods. Urine was obtained over 168 hours from 6 subjects who smoked low (15.8 mg) and high dose (33.8 mg) THC cigarettes on two occasions. Samples were analyzed for THCCOOH concentration by GC/MS and volume, time and creatinine concentration measured. A population pharmacokinetic model of the urinary clearance of THCCOOH was created from these data and potential covariates of urine creatinine concentration and urine creatinine excretion rate were assessed. Results. Elimination clearance of THCCOOH was estimated as 0.104 ± 0.088 L/min and its urinary clearance was 0.0022 ± 0.0015 L/min. Total urine excretion of THCCOOH was estimated a 2.3%. Urine flow rate and urine creatinine concentrations were significantly correlated, r2 0.35. Creatinine excretion rate was 129.6 ± 71.0 mL/min and the intra-subject variability was 31-52% (SD%) during the week. Urinary creatinine excretion rate was a significant covariate for the urinary clearance of THCCOOH. Conclusions. Creatinine Clearance is a significant covariate for urinary THCCOOH clearance. Only 2-3% of bioavailable THC is excreted as THCCOOH and THCCOO-glucuronide via the urine. Correction of urine drug and/or metabolite concentration with urine creatinine concentration or specific gravity may be more problematic than previously appreciated.