Gastric function and absorption
SUPPORTING DATA FROM A PHARMACOKINETIC STUDY IN ORTHOPEDIC SURGERYPetring et al28
STUDY DESIGN: This was a randomized, double-blind pharmacokinetic study involving 15 patients undergoing orthopedic surgery with spinal anesthesia. Patients were randomized to receive a single dose of intramuscular morphine 10 mg (n=8) or a single dose of intramuscular ketorolac 30 mg (n=7) for post-op pain. As a measure of liquid gastric emptying, oral acetaminophen solution at 20 mg/kg was administered to each patient at 2 time points, at least 12 hours before scheduled surgery (pre-op) and 30 minutes after the first administration of morphine or ketorolac (post-op).
Efficacy of acetaminophen was not assessed in this study.
Post-op gastric impairment can impact absorption of analgesics
Following surgery, compromised gastric function has been shown to diminish the absorption of oral analgesics
Mean pre-op and post-op plasma concentrations of oral acetaminophen
- Post-op plasma concentrations of oral acetaminophen (used as a measure of liquid gastric emptying) were significantly lower than pre-op values (P<0.001) in patients who received a single dose of morphine following surgery
- Post-op maximum concentration (Cmax) and time to reach maximum concentration (Tmax) of oral acetaminophen could not be determined following morphine administration due to a marked delay in absorption
SUPPORTING DATA FROM A PHARMACOKINETIC STUDY IN CARDIAC SURGERYBerger et al29
STUDY DESIGN: This was a prospective pharmacokinetic study conducted in patients with adequate hemodynamic status undergoing cardiac surgery (n=16), patients with hemodynamic failure undergoing cardiac surgery (n=23), and healthy volunteers who served as controls (n=6) to assess intestinal absorption as a function of hemodynamic status. To test the role of pyloric opening and assess intestinal absorption, 1 g of acetaminophen in liquid formulation was administered on post-op days 1 and 3 through a nasogastric or postpyloric tube.
Efficacy was not assessed in this study.
Opioid-related pyloric narrowing or closure led to decreased concentrations of oral acetaminophen
Peak plasma levels of oral acetaminophen on day 1
- Oral acetaminophen absorption was decreased following nasogastric, but not postpyloric, administration on day 1 post surgery
Several factors may diminish gastric function following surgery28-31
In the period immediately following surgery, gastroparesis and delayed gastric emptying may be caused by:
- Pre-op fasting
- Post-op stress
SUPPORTING DATA FROM A PHARMACOKINETIC STUDY IN HEALTHY SUBJECTSDevarakonda et al32
STUDY DESIGN: This was a randomized, single-blind, two-way, repeated-dose study in healthy adults to assess how opioids alter the pharmacokinetics of orally administered acetaminophen. Participants were randomly assigned to receive either 4 repeat doses of oral acetaminophen 1 g with IV placebo every 6 hours (n=11) or 4 repeat doses of IV acetaminophen 1 g with 2 placebo tablets every 6 hours (n=11). Both groups received 2 doses of IV morphine at 0.125 mg/kg at hours 6 and 12. The observed pharmacokinetic profiles of oral and IV acetaminophen were compared with their predicted profiles.
Efficacy was not assessed in this study.
Impact of morphine on the absorption of oral acetaminophen
A two-way, repeated-dose study in healthy adults assessed how opioids alter the pharmacokinetics of orally or intravenously administered acetaminophen
Group A: Oral acetaminophen plasma concentrations
- Group A: 4 repeat doses of oral acetaminophen 1 g with IV placebo and 2 doses of IV morphine at 0.125 mg/kg (n=11)
- Peak plasma levels of oral acetaminophen were diminished following IV morphine administration
- Time to reach maximum concentration (Tmax) was prolonged, and area under the curve from 0 to 6 hours (AUC0-6) was reduced
Group B: IV acetaminophen plasma concentrations
- Group B: 4 repeat doses of IV acetaminophen 1 g with tablet placebo and 2 doses of IV morphine at 0.125 mg/kg (n=11)
- Peak plasma levels of IV acetaminophen were similar before, during, and after IV morphine administration
- AUC0-6 was also similar
- Acetaminophen is contraindicated in patients with
- known hypersensitivity to acetaminophen or to any of the excipients in the intravenous formulation
- severe hepatic impairment or severe active liver disease