Changes in some serum biochemical parameters during two- and six-week use of therapeutic doses of opioids and in the early stages of drug withdrawal

Abstract

An important issue today is the safety of opioids for the treatment of chronic pain syndrome, which accompanies a number of somatic diseases. Most drugs or their metabolites are excreted through the kidneys and are one of the causes of acute and chronic kidney damage. The aim of the study was to compare some serum biochemical parameters of rats at two and six weeks of therapeutic doses of nalbuphine and to compare them after early withdrawal. This study was performed on 45 white sexually mature male rats weighing 180–260 g. In the serum of experimental animals’ total protein, urea, creatinine, calcium and phosphorus were determined. Statistical calculations were performed using RStudio v. 1.1.442 and R Commander v.2.4-4. Serum total protein in the study groups had small fluctuations in control, but there was a tendency to decrease after 2 weeks of nalbuphine administration and to increase both from the second to the sixth week and with the withdrawal of nalbuphine in the early stages of the experiment. Serum creatinine increased from the second to the sixth week of the experiment both with six weeks of administration (2.23 times higher than control values) and with two weeks of nalbuphine with the subsequent four-week withdrawal (1.63 times higher than control values). Serum urea increased after 2 weeks and 6 weeks of nalbuphine administration, with mean values 6.22 ± 0.47 mmol/l and 7.63 ± 0.74 mmol/l respectively. However, after drug withdrawal the indicator decreased to the control group. Serum calcium in rats decreased after 2 weeks of the experiment to the value (2.16 ± 0.09 mmol/l). After 6 weeks of nalbuphine administration, as after drug withdrawal, serum calcium increased to the level of the control group and was 2.39 ± 0.09 mmol/l and 2.46 ± 0.05 mmol/l respectively. The serum phosphorus index increased after 2 weeks of the experiment and was 2.42 ± 0.05 mmol/l. After 6 weeks of nalbuphine administration and after drug withdrawal, the value decreased to 2.12 ± 0.12 mmol/l and 2.00 ± 0.05 mmol/l respectively. Conclusions. The use of therapeutic doses of nalbuphine for two and six weeks, as well as after drug withdrawal does not affect the concentration of serum total protein of rats. As a result of two- and six-week use of the drug, an impaired renal nitrogen excretion is observed, and hence the structure of the renal corpuscles is altered, which also takes place during four weeks of drug withdrawal after two weeks of use, as evidenced by an increase in urea and creatinine after two weeks of nalbuphine and significant increase in creatinine after drug withdrawal. Two-week administration of nalbuphine leads to hypocalcemia and hyperphosphatemia, indicating impaired renal reabsorption function, while a subsequent four-week administration and withdrawal leads to normalization of these parameters, except for phosphorus, which is reduced.