Recent advances in the translation of drug metabolism and pharmacokinetics science for drug discovery and development

Drug metabolism and pharmacokinetics (DMPK) is an important branch of pharmaceutical sciences. The nature of ADME (absorption, distribution, metabolism, excretion) and PK (pharmacokinetics) inquiries during drug discovery and development has evolved in recent years from being largely descriptive to seeking a more quantitative and mechanistic understanding of the fate of drug candidates in biological systems. Tremendous progress has been made in the past decade, not only in the characterization of physiochemical properties of drugs that influence their ADME, target organ exposure, and toxicity, but also in the identification of design principles that can minimize drug-drug interaction (DDI) potentials and reduce the attritions. The importance of membrane transporters in drug disposition, efficacy, and safety, as well as the interplay with metabolic processes, has been increasingly recognized. Dramatic increases in investments on new modalities beyond traditional small and large molecule drugs, such as peptides, oligonucleotides, and antibody-drug conjugates, necessitated further innovations in bioanalytical and experimental tools for the characterization of their ADME properties. In this review, we highlight some of the most notable advances in the last decade, and provide future perspectives on potential major breakthroughs and innovations in the translation of DMPK science in various stages of drug discovery and development.

Clinical study of the combination of acupoint catgut-embedding therapy and auricular point pressure in the treatment of insomnia of spleen and stomach disharmony pattern / 中国针灸

<p><b>OBJECTIVE</b>To observe the differences in the clinical therapeutic effects on insomnia of spleen and stomach disharmony pattern in comparison of the combination of acupoint catgut-embedding therapy and auricular point pressure with the simple application of auricular point pressure.</p><p><b>METHODS</b>One hundred and eighty patients of insomnia of spleen and stomach disharmony pattern were randomized into an observation group (93 cases) and a control group (87 cases). In the observation group, the combination of acupoint catgut-embedding therapy and auricular point pressure was adopted. The acupoint catgut-embedding therapy was applied at Zhongwan (CV 12), Anmian (Extra), Xinshu (BL 15), Pishu (BL 20), Weishu (BL 21), Zusanli (ST 36), Yinlingquan (SP 9) and Sanyinjiao (SP 6), once every two weeks. The auricular point pressure was applied to Shenmen (TF), Pizhixia (AT), Xin (CO), Pi (CO), Wei (CO) on both sides alternatively, twice a week. The duration of treatment was 2 months for the two groups. In the control group, the auricular point pressure was simply used with the same points, manipulation and treatment duration as the observation group. After treatment, the clinical therapeutic effects were observed in the patients of the two groups. The Pittsburgh sleep quality index (PSQI) score was compared before and after treatment in the two groups. The recurrence was followed up in 3 months after the end of treatment.</p><p><b>RESULTS</b>It was observed that 2 cases were dropped out in the observation group, 4 cases in the control group. The dropped out cases were considered to be ineffective. After treatment, the total effective rate was 92.5% (86/93) in the observation group and was 80.5% (70/87) in the control group. The result in the observation group was better than that in the control group (<0.05). After treatment, PSQI scores were all reduced apparently in the two groups as compared with those before treatment (both<0.05). The score after treatment and the different value before and after treatment in the observation group were lower than those in the control group (both<0.05). In 3-month follow-up after treatment, the recurrence rate was 3.2% (3/93) in the observation group, which was lower than 13.8% (12/87) in the control group (<0.05).</p><p><b>CONCLUSION</b>In the treatment of insomnia of spleen and stomach disharmony pattern, the acupoint catgut-embedding therapy combined with auricular point pressure are superior to the simple application of auricular point pressure in the clinical therapeutic effects, improving sleep quality and reducing the recurrence rate.</p>

The change of negative pressure in the cupping-cup and its influence on the depth of filiform-needle insertion / 生物医学工程学杂志

This study was designed to observe the negative pressure in the cup during cupping, and to investigate the influence of negative pressure on the depth of filiform-needle inserted and retained. In the beginning, the change of pressure after cupping on acupoint BL23 for a span of 20 minutes was recorded. Acupuncture on acupoint BL23 was performed; the filiform-needle was retained and followed by cupping at different levels of negative pressure, and the changes of the depth of needle insertion was measured. The results showed: the absolute value of the negative pressure in the cup goes down with time and is significantly lower after 20 minutes (P < 0.05); the negative pressure in the cup causes the retreat of the inserted needle; and under the same pressure, there is a greater length measurement in needle retreat for male than for female (P < 0.01). The length of needle retreat is related to the pressure in the cupping-cup and to gender.

Effects of Tangxinping Capsule on angiotensin II and its type 1 receptor and myocardial ultrastructure in diabetic rats / 中西医结合学报

To investigate the protective effects of Tangxinping Capsule, a compound traditional Chinese herbal medicine, on diabetic cardiomyopathy in rats.