Clinical pharmacology of phlebotropic drugs.

Methods used in clinical and clinical pharmacological assessments of phlebotropic drugs are outlined. The knowledge of the pharmacokinetics and metabolism of phlebotropic drugs in human organism is far from complete as yet. Of objective methods proving haemodynamic effects of phlebotropic drugs, the authors have the best experiences with the strain-gauge type occlusive plethysmography, which is capable of proving a reduction of the capillary filtration fraction even after a single administration of an active preparation to healthy volunteers. The control of the patient's subjective complaints by phlebotropic drugs is documented by statistically significant findings in double-blind clinical trials with a placebo.     

Clinical pharmacology studies with Centchroman.

A pharmacological evaluation of centchroman (3,4-trans-2,2,dimethyl-3-phenyl-4-p-(beta-pyrrolidino ethoxy)-phenyl-7-methoxychroman), a new postcoital contraceptive, in normal healthy human volunteers was performed to determine the maximum tolerated dose and to discover any abnormal toxic effects in humans. The study was carried out for both men and women as a double-blind noncrossover trial in 2 parts: 1) a single dose study (40 volunteers) and 2) a multiple dose study (28 females) for 30 days. Centchroman was well tolerated without significant side effects in single doses up to 320 mg, severalfold higher than the anticipated therapeutic dose. In the multiple dose schedule, the compound was found safe at doses of 60-120 mg/day. however, similar effects were observed in subjects receiving placebo and are not unexpected in a normal population over a 1-month period. Centchroman is presently undergoing clinical trials for postcoital contraceptive efficacy in humans.     

Clinical advances of siRNA therapeutics

Small interfering RNA (siRNA) enables efficient target gene silencing by employing a RNA interference (RNAi) mechanism, which can compromise gene expression and regulate gene activity by cleaving mRNA or repressing its translation. Twenty years after the discovery of RNAi in 1998, ONPATTRO? (patisiran) (Alnylam Pharmaceuticals, Inc.), a lipid formulated siRNA modality, was approved for the first time by United States Food and Drug Administration and the European Commission in 2018. With this milestone achievement, siRNA therapeutics will soar in the coming years. Here, we review the discovery and the mechanisms of RNAi, briefly describe the delivery technologies of siRNA, and summarize recent clinical advances of siRNA therapeutics.