• DOI:10.1124/dmd.108.024000
• Corpus ID: 15150118

Cannabinoid Receptor Agonist 13, a Novel Cannabinoid Agonist: First in Human Pharmacokinetics and Safety

@article{Gardin2009CannabinoidRA,
  title={Cannabinoid Receptor Agonist 13, a Novel Cannabinoid Agonist: First in Human Pharmacokinetics and Safety},
  author={Anne Gardin and Klaus Kucher and Beate Kiese and Silke Appel-Dingemanse},
  journal={Drug Metabolism and Disposition},
  year={2009},
  volume={37},
  pages={827 - 833}
}

• A. Gardin, K. Kucher, +1 author S. Appel-Dingemanse
• Published 1 April 2009
• Medicine, Biology
• Drug Metabolism and Disposition

Cannabinoid receptor agonist 13 (CRA13) is a novel cannabinoid (CB) receptor agonist with high affinity and functional activity toward both CB1 and CB2 receptors. This phase I study aimed to evaluate the pharmacokinetics, safety, and tolerability of single oral doses of CRA13. Sixty-three of 69 healthy adult males were randomized in seven cohorts (n = 9) to receive 1 to 80 mg of CRA13 or placebo orally in fasted condition. To investigate the diet effect, an independent group (n = 6) was randomized to receive 40 mg of CRA13 after high-fat and high-calorie breakfast in crossover design with a 2-week washout period. Peak plasma concentration (Cmax) ranged from 7.8 to 467.6 ng/ml (1–80 mg). CRA13 was rapidly absorbed and demonstrated linear pharmacokinetics (1–80 mg). Time to reach Cmax (tmax) was 1.5 to 2 h for all doses in both fasted and fed groups. Administration of 40 mg of CRA13 with food induced approximately 2-fold increase in the Cmax and the area under the concentration-time curve, AUC0 – tz. The apparent elimination half-life (t1/2) was 21 to 36 h and 30 to 41 h for fasted and fed groups, respectively. Dizziness, headache, and nausea were the most frequently reported adverse events (AEs), predominantly at the 40- and 80-mg doses. The incidence of AEs was dose-dependent and mild to moderate. No deaths and serious adverse events were reported. In conclusion, CRA13 was reasonably well tolerated and demonstrated a linear pharmacokinetics over the studied dose range (1–80 mg). Food intake increased CRA13 Cmax and AUC0 – tz by approximately 2-fold, whereas tmax was unaffected.