PMID- 19144772
OWN - NLM
STAT- MEDLINE
DCOM- 20090714
LR  - 20121115
IS  - 1521-009X (Electronic)
IS  - 0090-9556 (Linking)
VI  - 37
IP  - 4
DP  - 2009 Apr
TI  - Cannabinoid receptor agonist 13, a novel cannabinoid agonist: first in human 
      pharmacokinetics and safety.
PG  - 827-33
LID - 10.1124/dmd.108.024000 [doi]
AB  - Cannabinoid receptor agonist 13 (CRA13) is a novel cannabinoid (CB) receptor 
      agonist with high affinity and functional activity toward both CB(1) and CB(2) 
      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 (C(max)) 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 C(max) (t(max)) 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 C(max) and the area under the concentration-time curve, AUC(0 - tz). The 
      apparent elimination half-life (t(1/2)) 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 C(max) and AUC(0 - tz) by 
      approximately 2-fold, whereas t(max) was unaffected.
FAU - Gardin, Anne
AU  - Gardin A
AD  - Novartis Institutes for BioMedical Research, Basel, CH-4002, Switzerland. 
      anne.gardin@novartis.com
FAU - Kucher, Klaus
AU  - Kucher K
FAU - Kiese, Beate
AU  - Kiese B
FAU - Appel-Dingemanse, Silke
AU  - Appel-Dingemanse S
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20090114
PL  - United States
TA  - Drug Metab Dispos
JT  - Drug metabolism and disposition: the biological fate of chemicals
JID - 9421550
RN  - 0 (Cannabinoid Receptor Agonists)
RN  - 0 (Naphthalenes)
RN  - 0 (Placebos)
RN  - 0 (cannabinoid receptor agonist 13)
SB  - IM
MH  - Area Under Curve
MH  - *Cannabinoid Receptor Agonists
MH  - Cohort Studies
MH  - Double-Blind Method
MH  - Half-Life
MH  - Humans
MH  - Male
MH  - Naphthalenes/*adverse effects/*pharmacokinetics/pharmacology
MH  - Placebos
EDAT- 2009/01/16 09:00
MHDA- 2009/07/15 09:00
CRDT- 2009/01/16 09:00
PHST- 2009/01/16 09:00 [entrez]
PHST- 2009/01/16 09:00 [pubmed]
PHST- 2009/07/15 09:00 [medline]
AID - dmd.108.024000 [pii]
AID - 10.1124/dmd.108.024000 [doi]
PST - ppublish
SO  - Drug Metab Dispos. 2009 Apr;37(4):827-33. doi: 10.1124/dmd.108.024000. Epub 2009 
      Jan 14.