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  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.
The pharmacokinetics of oral ketoprofen in patients after gastric resection.Pharmacol Rep. 2017 Apr;69(2):296-299. doi: 10.1016/j.pharep.2016.11.010. Epub 2016 Dec 9. Pharmacol Rep. 2017. PMID: 28178590
The pharmacokinetics, metabolism and urinary detection time of tramadol in camels.Vet J. 2008 Nov;178(2):272-7. doi: 10.1016/j.tvjl.2007.07.008. Epub 2007 Sep 29. Vet J. 2008. PMID: 17904881
Influence of Obesity and Type 2 Diabetes Mellitus on the Pharmacokinetics of Tramadol After Single Oral Dose Administration.Eur J Drug Metab Pharmacokinet. 2019 Aug;44(4):579-584. doi: 10.1007/s13318-019-00543-1. Eur J Drug Metab Pharmacokinet. 2019. PMID: 30778911 Free PMC article.
Evaluation of the route dependency of the pharmacokinetics and neuro-pharmacokinetics of tramadol and its main metabolites in rats.Eur J Pharm Sci. 2016 Sep 20;92:55-63. doi: 10.1016/j.ejps.2016.06.021. Epub 2016 Jun 27. Eur J Pharm Sci. 2016. PMID: 27365222
Pharmacokinetics of paracetamol in patients with chronic pancreatitis.Pharmacol Rep. 2016 Aug;68(4):733-6. doi: 10.1016/j.pharep.2016.03.010. Epub 2016 Mar 23. Pharmacol Rep. 2016. PMID: 27127912