A peer-reviewed, evidence-based journal that promotes clinical development and metabolic insights in total bariatric patient care for the healthcare professional
Issue link: https://bariatrictimes.epubxp.com/i/295392
A4 Bariatric Times [MAY 2014, SUPPLEMENT A] HOT TOPICS IN SURGICAL PAIN MANAGEMENT Clinical Pharmacology of OFIRMEV The pharmacokinetics and pharmacodynamics of IV acetaminophen have been well characterized (Figure 1). 16,17 In a pharmacokinetic study conducted by Cadence Pharmaceuticals, Inc., IV acetaminophen was compared to oral acetaminophen. 16 Compared with a 1g dose of oral acetaminophen, 1g of IV acetaminophen shows up to 70 percent higher maximum plasma concentration (C max ), with a median time to reach C max (T max ) at 15 minutes (end of infusion). Area under the concentration-time curve (AUC) is very similar for the same dose of IV acetaminophen and oral acetaminophen. 16 The peak effect of 1g acetaminophen occurs within one hour of administration and duration of effect is 4 to 6 hours. 18 Additionally, there is no evidence of clinically significant drug accumulation with repeated dosing. 19 In a second pharmacokinetic study by Singla and colleagues, the plasma and cerebrospinal fluid (CSF) pharmacokinetics of IV, oral, and rectal acetaminophen were compared. Six healthy male subjects were included in a three-way, crossover, single-center, single-dose design pharmacokinetic study. The IV route produced 76 percent higher mean plasma C max (P=0.0004) than oral and a 256 percent higher C max (P<0.0001) than rectal administration of acetaminophen (Figure 1a). The T m ax for the IV route was earlier (0.25 hours) than that for the oral route (1 hour, P=0.0018) or the rectal route (2.5 hours, P=0.0025). 17 In this study, the mean CSF AUC for IV acetaminophen over six hours was 75 percent higher than the oral AUC (P=0.0099) and 142 percent higher than the rectal AUC (P=0.0004). The mean CSF C max value for IV acetaminophen was 59.7 percent higher than that for oral (P<0.0001) and 86.8 percent higher than that for rectal administration (P<0.0001) (Figure 1b). 17 Clinical Considerations Regarding Route of Administration Surgery, opioids, anesthesia, preoperative fasting, and postoperative stress can all work together in the immediate postoperative period to produce gastroparesis and delayed gastric emptying (Figure 2). These factors are important when choosing the appropriate formulation of acetaminophen in the perioperative setting, as absorption of oral analgesics may be compromised in the immediate postoperative setting. 20–23 Following surgery, compromised gastric function has been shown to diminish the absorption of oral acetaminophen. In a prospective pharmacokinetic study designed to assess absorption, Berger and colleagues demonstrated that opiate-related pyloric narrowing or closure leads to decreased plasma concentrations of acetaminophen given orally. 21 FIGURE 1. Pharmacokinetic study of acetaminophen—plasma and CSF levels Randomized, three-way, crossover design in six healthy volunteers; efficacy was not assessed. *Note: Rectal acetaminophen data reflect standardization of the 1,300-mg dose to 1,000 mg (linear kinetics). Singla NK, et al. Pain Pract. 2012;12:523-532. FIGURE 2. Absorption of oral analgesics may be compromised in the perioperative setting a b EDITED-Cadence Ofirmez Suppl copy 2_Layout 1 4/14/14 10:14 AM Page A4