Ketoprofen and tramadol pharmacokinetics in patients with chronic pancreatitis

Eur Rev Med Pharmacol Sci. 2019 May;23(9):4044-4051. doi: 10.26355/eurrev_201905_17835.


Objective: Chronic pancreatitis (CP) is a disease leading to irreversible pancreas dysfunction. One of the main symptoms is pain. Many patients require pharmacological therapy which should be started with paracetamol or, in selected groups of patients, ketoprofen. If the effect of ketoprofen is irrelevant, patients receive tramadol. The aim of this study is the evaluation of ketoprofen and tramadol pharmacokinetics (PK) in CP patients.

Patients and methods: 36 patients were divided into two groups: I - receiving ketoprofen (n=18; mean [SD] age, 48.61 [13.32] years; weight, 73.28 [20.48] kg), II - receiving tramadol (n=18; mean [SD] age, 46.78 [10.28] years; weight, 74.22 [14.04] kg, and BMI (Body Mass Index), 24.61 [4.51] kg/m2). The plasma concentrations of ketoprofen and tramadol with its active metabolite M1 (0-desmethyltramadol) were measured with the validated high-performance liquid chromatography method.

Results: The main PK parameters for ketoprofen were as follows: Cmax (maximum plasma concentration), 3.41 [2.32] mg/L; AUC0-inf (area under the plasma concentration-time curve from time zero to infinity), 10.45 [5.57] mg⋅h/L; tmax (time to first occurrence of Cmax), 1.94 [1.25] h; Cl (clearance), 0.199 [0.165] L/kg·h, and Vd/kg (volume of distribution per kilogram of body weight), 0.71 [0.58] L/kg. The main PK parameters for TRM and M1 were as follows: Cmax, 226.4 [80.5] and 55.6 [23] ng/mL; AUC0-inf, 1903.3 [874.8] and 790.4 [512.4] ng⋅h/mL; tmax, 1.78 [0.73] and 2.67 [1.19] h, respectively.

Conclusions: Chronic pancreatitis led to a decrease in the total amount of absorbed ketoprofen. Consequently, the analgesic effect of the drug may be weaker. Cmax of tramadol for most CP patients was within the therapeutic range associated with its analgesic activity. M1/TRM ratios for Cmax and AUC were unchanged.

MeSH terms

  • Adult
  • Analgesics, Opioid / blood
  • Analgesics, Opioid / pharmacokinetics
  • Analgesics, Opioid / therapeutic use*
  • Anti-Inflammatory Agents, Non-Steroidal / blood
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacokinetics
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Area Under Curve
  • Chromatography, High Pressure Liquid
  • Female
  • Half-Life
  • Humans
  • Ketoprofen / blood
  • Ketoprofen / pharmacokinetics
  • Ketoprofen / therapeutic use*
  • Male
  • Middle Aged
  • Pancreatitis, Chronic / drug therapy*
  • Pancreatitis, Chronic / metabolism
  • ROC Curve
  • Tramadol / blood
  • Tramadol / pharmacokinetics
  • Tramadol / therapeutic use*


  • Analgesics, Opioid
  • Anti-Inflammatory Agents, Non-Steroidal
  • Tramadol
  • Ketoprofen