Dh. Beck et al., The pharmacokinetics and analgesic efficacy of larger dose rectal acetaminophen (40 mg/kg) in adults: A double-blinded, randomized study, ANESTH ANAL, 90(2), 2000, pp. 431-436
Citations number
17
Categorie Soggetti
Aneshtesia & Intensive Care","Medical Research Diagnosis & Treatment
Analgesic acetaminophen plasma concentrations are not known. We investigate
d in a randomized, double-blinded study the pharmacokinetics and analgesic
efficacy of small- (AS;20 mg . kg(-1)) and larger- (AL;40 mg/kg) dose recta
l acetaminophen and compared it with the combination (C) of rectal diclofen
ac (100 mg) and acetaminophen (20 mg/kg) in 65 women undergoing hysterectom
y. Suppositories were administered after the induction of a standardized ge
neral anesthesia. Pain (measured by using a 10-cm visual analog scale) and
morphine consumption (patient-controlled analgesia) were repeatedly assesse
d for 24 h. Acetaminophen plasma concentrations were measured by using a fl
uorescence polarization immunoassay. Antipyretic plasma concentrations (10-
20 mg/L) after 40 mg/kg acetaminophen were not associated with improved ana
lgesia or decreased opioid requirements; 20 mg/kg acetaminophen produced su
btherapeutic plasma levels (<10 mg/L). Maximal plasma concentrations of 17.
2 and 10.4 mg/L (P < 0.01, analysis of variance) were achieved after 4.2 an
d 3.6 h for the AL and AS groups, respectively. The only difference in clin
ical outcome was lower visual analog scale scores after acetaminophen/diclo
fenac (C: 2.0 versus AS: 3.2 and AL: 3.4) 4 h after the induction (P < 0.05
, analysis of variance). Acetaminophen pharmacokinetics in adults were simi
lar to those observed in children. Analgesic plasma concentrations are like
ly to be higher than antipyretic plasma levels, which were only attained af
ter twice the recommended rectal dose was administered. Analgesic plasma co
ncentrations have yet to be determined but may be higher than those associa
ted with antipyresis. Implications: Acetaminophen pharmacokinetics were com
parable in adults and children. Plasma concentrations known to reduce fever
did not produce better pain relief and were only achieved after twice the
conventional dose was administered. Analgesic plasma concentrations have ye
t to be determined but may be higher than those associated with antipyresis
.