DETERMINATION OF TAMSULOSIN HYDROCHLORIDE RELEASE PHARMACOKINETICS IN PROSTATE GLAND BY A RADIOTRACER METHOD

Abstract

Introduction: recently in Ukraine prostate diseases have taken one of the leading places among male urological pathologies. Prostate gland hyperplasia is one of the most common ones. Causes of hyperplasia have not been reliably established so far, however, it has been proved that the poor state of androgen production in men is an integral condition for the development of benign prostatic hyperplasia. One of the urgent tasks of modern pharmaceutical science is to create new high-performance drugs in such dosage forms that provide optimal therapeutic effect with minimal adverse complications. Among a large number of drugs for the treatment of prostate diseases a prominent place is occupied by alpha-adrenoblockers – drugs of the first-line treatments that affect the α1А-adrenergic receptors, reduce or completely eliminate the muscle tone of the prostatic urethra and bladder neck. Tamsulosin hydrochloride is a selective and competitive blocker of postsynaptic α1А-adrenergic receptors. The selectivity of tamsulosin to α1А-adrenergic receptors, which are located in the bladder, is 20 times greater than its ability to interact with α1В-adrenoceptors that are located in vascular smooth muscles. Objective: to study the pharmacokinetics of tamsulosin hydrochloride release into prostate gland after oral and rectal administration by a radioactive-tracer technique. Materials and methods of research: tamsulosin hydrochloride substance and suppositories with this substance labeled by 14С with a specific activity of 3.7× 107Bq/mg. Pharmacokinetic studies of tamsulosin hydrochloride in the prostate were performed after oral and rectal administration. The experiments were carried out on white mature male rats of Wistar line weighing 210 ± 10 g. Pharmacokinetic studies were performed using a radioactive-tracer technique (tracers) after oral and rectal administration of tamsulosin. Results and their discussion: after rectal administration the release of tamsulosin hydrochloride is more complete and intensive compared to oral route of administration. Thus, the results of the experiment prove that the preparation reaches the prostate much faster, releases more completely and has a higher bioavailability. Conclusions: the study of pharmacokinetics of tamsulosin hydrochloride accumulation in prostate gland after oral and rectal administration by a radioactive-tracer technique with the help of α-β-radiometer NRR-610 “Tesla” has been done. The research results proved the advantages of rectal route of drug administration compared with oral. The obtained results confirm the expediency of creation of the medicinal preparation with alpha-adrenoblocker tamsulosin hydrochloride in the form of suppositories for prostate diseases treatment.

Keywords

• suppositories
• pharmacokinetics
• α – adrenogenic blockers