TAPENTADOL AND TOBACCO SMOKING - A PHARMACOKINETIC AND PHARMACODYNAMIC STUDY IN PATIENTS AFTER OPEN ABDOMINAL HYSTERECTOMY - A PILOT STUDY

Tapentadol (TAP) is the first representative of a new class of multimodal analgesics with a favorable safety profile, also applicable in postoperative pain. As a UDP-glucuronosyltransferase (UGT) substrate (in about 70%), TAP pharmacokinetics can potentially be influenced by UGT inducers or inhibitors. It is known that smoking can increase drug metabolism activity through UGT enzyme induction. Therefore, the study aimed to evaluate the pharmacokinetics of TAP after open abdominal hysterectomy (AH) in smoking compared to non-smoking tobacco patients. A single oral dose of TAP 100 mg was given to the patients on the first postoperative day after AH (n = 6, smoking and n = 8, non-smoking patients). Pain relief (Numerical Rating Scale, NRS), sedation, saturation, heart rate, and adverse effects were monitored. Blood samples were collected within 12 h after the drug administration. Smokers presented significantly lower C-max and AUC(0-t), and CL/F value was twice as high in this group. A moderately strong negative correlation between NRS scores and TAP concentration was revealed (R-2=-0.5231). Negative correlations between TAP concentration and life parameters: oxygen saturation and heart rate were observed. Significantly lower plasma concentrations and exposure to TAP in smoking patients after AH compared to non-smoking may indicate metabolic induction of UDP-glucuronosyltransferase by components of tobacco smoke. Since plasma concentration of TAP and NRS are negatively correlated, this may require consideration of TAP dose adjustments in smoking patients.