Pharmacokinetics comparison of vardenafil as administered by an intranasal spray formulation vs a 10-mg oral tablet.

Background: Oral vardenafil (VDF) tablet is an effective treatment for erectile dysfunction (ED), but intranasal administration with a suitable formulation can lead to a faster onset of action and offer more convenient planning for ED treatment.

Aim: The primary purpose of the present pilot clinical study was to determine whether intranasal VDF with an alcohol-based formulation can result in more "user-friendly pharmacokinetics" as compared with oral tablet administration.

Methods: This single-dose randomized crossover study was conducted in 12 healthy young volunteers receiving VDF as a 10-mg oral tablet or 3.

Use of conditional reprogramming cell, patient derived xenograft and organoid for drug screening for individualized prostate cancer therapy: Current and future perspectives (Review).

Prostate cancer mortality is ranked second among all cancer mortalities in men worldwide. There is a great need for a method of efficient drug screening for precision therapy, especially for patients with existing drug‑resistant prostate cancer. Based on the concept of bacterial cell culture and drug sensitivity testing, the traditional approach of cancer drug screening is inadequate.

Development of a simple and rapid HPLC-MS/MS method for quantification of streptomycin in mice and its application to plasma pharmacokinetic studies.

Streptomycin was the first discovered aminoglycoside antibiotic. It has been widely applied in veterinary medicine for the prevention and treatment of bacterial infection. However, the current detection methods are not satisfactory in terms of sensitivity and sample process, which makes them unsuitable for a pharmacokinetic study.

Follow that botanical: Challenges and recommendations for assessing absorption, distribution, metabolism and excretion of botanical dietary supplements.

Botanical dietary supplements are complex mixtures containing one or more botanical ingredient(s), each containing numerous constituents potentially responsible for its purported biological activity. Absorption, distribution, metabolism, and excretion (ADME) data are critical to understand the safety of botanical dietary supplements, including their potential for pharmacokinetic botanical-drug or botanical-botanical interactions. However, ADME data for botanical dietary supplements are rarely available and frequently inadequate to characterize their fate in vivo.

Bioavailability of wilforlide A in mice and its concentration determination using an HPLC-APCI-MS/MS method.

Wilforlide A (WA), an active compound in Tripterygium wilfordii Hook F (TW) which is a traditional Chinese medicine for treatment of autoimmune diseases, is a quality control marker for TW product. At present, the bioavailability/pharmacokinetics of WA is not known. Such information is not only essential to evaluate the relevance of WA as a quality control maker, but also important for future clinical efficacy studies.

A simple and sensitive HPLC-MS/MS method for quantification of eggmanone in rat plasma and its application to pharmacokinetics.

Allosteric phosphodiesterase 4 (PDE4) inhibitors are highly sought after due to their important anti-inflammatory and anti-cancer therapeutic effects. We recently identified Eggmanone, an extraordinarily selective allosteric PDE4 inhibitor displaying favorable drug properties. However, a specific analytic method of Eggmanone in serum and its pharmacokinetics have not been reported yet.

Enhanced anti-tumor efficacy and mechanisms associated with docetaxel-piperine combination- and investigation using a taxane-resistant prostate cancer model.

Docetaxel (DTX) is widely used for metastatic castrated resistant prostate cancer, but its efficacy is often compromised by drug resistance associated with low intracellular concentrations. Piperine (PIP) could enhance the bioavailability of other drugs via the inhibition of CYPs and P-gp activities. Thus, we hypothesize a positive effect with the DTX-PIP combination on the anti-tumor efficacy and intra-tumor DTX concentrations in taxane-resistant prostate cancer.

Overcoming chemoresistance in prostate cancer with Chinese medicine Tripterygium wilfordii via multiple mechanisms.

A leading cause of cancer chemotherapy failure is chemoresistance, which often involves multiple mechanisms. Chinese medicines (CM) usually contain multiple components which could potentially target many mechanisms simultaneously and may offer an advantage over single compounds that target one mechanism at a time. The purpose of this study was to investigate the chemosensitizing effect (CE) of a specific CM, Tripterygium wilfordii (TW), on prostate cancer cells resistant to docetaxel (Dtx) and identify the potential mechanisms.

Precision or Personalized Medicine for Cancer Chemotherapy: Is there a Role for Herbal Medicine.

Although over 100 chemotherapeutic agents are currently available for the treatment of cancer patients, the overall long term clinical benefit is disappointing due to the lack of effectiveness or severe side effects from these agents. In order to improve the therapeutic outcome, a new approach called precision medicine or personalized medicine has been proposed and initiated by the U.S.

Non-linear pharmacokinetics of piperine and its herb-drug interactions with docetaxel in Sprague-Dawley rats.

Piperine (PIP), the major alkaloid component from Piper longum L. and Piper nigrum L., could enhance the bioavailabilities of other drugs including rosuvastatin, peurarin and docetaxel (DOX) via inhibition of CYP3A and P-glycoprotein activity.

Molecular signatures in the prevention of radiation damage by the synergistic effect of N-acetyl cysteine and qingre liyan decoction, a traditional chinese medicine, using a 3-dimensional cell culture model of oral mucositis.

Qingre Liyan decoction (QYD), a Traditional Chinese medicine, and N-acetyl cysteine (NAC) have been used to prevent radiation induced mucositis. This work evaluates the protective mechanisms of QYD, NAC, and their combination (NAC-QYD) at the cellular and transcriptional level. A validated organotypic model of oral mucosal consisting of a three-dimensional (3D) cell tissue-culture of primary human keratinocytes exposed to X-ray irradiation was used.

Overview and appraisal of the current concept and technologies for improvement of sublingual drug delivery.

Sublingual drug delivery is capable of achieving high bioavailability by avoiding first-pass liver extraction and enzymatic degradation in the gastrointestinal tract, as well as achieving rapid onset of effect. Thus, this route of administration can offer attractive therapeutic advantages for certain drugs as a convenient substitute for parenteral administration and has been applied successfully to a number of therapeutic conditions, especially urgent cardiovascular conditions and acute severe pain control. However, due to inherent limitations such as small sublingual mucosa area for absorption, primarily passive mechanism of transport, short residence time, and potential local irritation, a relatively small number of sublingual products have been successfully developed to date.

Ginseng and anticancer drug combination to improve cancer chemotherapy: a critical review.

Ginseng, a well-known herb, is often used in combination with anticancer drugs to enhance chemotherapy. Its wide usage as well as many documentations are often cited to support its clinical benefit of such combination therapy. However the literature based on objective evidence to make such recommendation is still lacking.

Bench to bed evidences for pharmacokinetic and pharmacodynamic interactions involving oseltamivir and chinese medicine.

Oseltamivir (OA), an ethyl ester prodrug of oseltamivir carboxylate (OC), is clinically used as a potent and selective inhibitor of neuraminidase. Chinese medicines have been advocated to combine with conventional drug for avian influenza. The current study aims to investigate the potential pharmacokinetic and pharmacodynamic interactions of a Chinese medicine formula, namely, Yin Qiao San and Sang Ju Yin (CMF1), commonly used for anti-influenza in combination with OA in both rat and human, and to reveal the underlined mechanisms.

Traditional Chinese medicinal formula Si-Wu-Tang prevents oxidative damage by activating Nrf2-mediated detoxifying/antioxidant genes.

Background: Induction of Nrf2-mediated detoxifying/antioxidant genes has been recognized as an effective strategy for cancer chemoprevention. Si-Wu-Tang (SWT), comprising the combination of four herbs, Paeoniae, Angelicae, Chuanxiong and Rehmanniae, is one of the most popular traditional oriental medicines for women's diseases. The purpose of this study is to determine the effects of SWT on Nrf2 pathway in vitro and in vivo and to identify the active component(s).

Nutraceuticals for prostate cancer chemoprevention: from molecular mechanisms to clinical application.

Introduction: Nutraceutical is a food, or part of a food, used for the prevention and/or treatment of diseases. A number of nutraceuticals serve as candidates for development of prostate cancer chemopreventive agents because of promising epidemiological, preclinical and pilot clinical findings. Their mechanisms of action may involve an ability to target multiple molecular pathways in carcinogenesis without eliciting toxic side effects.

Bioavailability enhancement of glucosamine hydrochloride by chitosan.

Glucosamine, as a dietary supplement for management of osteoarthritis, has a low and erratic oral bioavailability due to its transport-mediated absorption and presystemic loss in liver and GI tract. The present study described an effective approach to improve glucosamine intestinal absorption and hence its bioavailability using chitosan. Effects of chitosan on intestinal permeability and pharmacokinetics of glucosamine were evaluated in Caco-2 cell monolayer and rats, respectively.

Utilization of gene expression signature for quality control of traditional Chinese medicine formula Si-Wu-Tang.

The current study utilized a combined pharmacokinetic and genomic approach to demonstrate the feasibility of a new quality control method by using a panel of special differentially expressed genes (DEGs) as unique fingerprint to serve as marker of in vivo bioactivity for a representative traditional Chinese medicine (TCM) formula, Si-Wu-Tang (SWT). The method involves firstly obtaining possible in vivo active components, i.e.

Herb-herb combination for therapeutic enhancement and advancement: theory, practice and future perspectives.

Herb-herb combinations have been used in Chinese medicine practice for thousands of years, yet scientific evidence of their therapeutic benefits is lacking. With increasing interest in shifting from the one-drug-one-target paradigm to combination therapy or polypharmacy to achieve therapeutic benefits for a number of diseases, there is momentum to explore new knowledge by tapping the past empirical experiences of herb-herb combinations. This review presents an overview of the traditional concept and practice of herb-herb combination in Chinese medicine, and highlights the available scientific and clinical evidence to support the combined use of herbs.

Clinical pharmacokinetics of buffered propranolol sublingual tablet (Promptol™)-application of a new "physiologically based" model to assess absorption and disposition.

Sublingual administration of certain buffered propranolol may improve the rate and extent of absorption compared to oral administration. The main objectives of this study were to (1) compare the plasma propranolol concentrations (Cp-prop) following sublingual administration of a specially buffered formulation (Promptol™) to that following oral administration of Inderal(®) and (2) evaluate the utility of a special pharmacokinetic model in describing the Cp-prop following sublingual administration. Eighteen healthy volunteers received 10 mg sublingual Promptol™ or oral Inderal(®).

Transcriptional profiling of Chinese medicinal formula Si-Wu-Tang on breast cancer cells reveals phytoestrogenic activity.

Background: Si-Wu-Tang (SWT), comprising the combination of four herbs, Paeoniae, Angelicae, Chuanxiong and Rehmanniae, is one of the most popular traditional oriental medicines for women's diseases. In our previous study, the microarray gene expression profiles of SWT on breast cancer cell line MCF-7 were found similar to the effect of β-estradiol (E2) on MCF-7 cells in the Connectivity Map database.

Methods: Further data analysis was conducted to find the main similarities and differences between the effects of SWT and E2 on MCF-7 gene expression.

CYP2C19 genotype has a major influence on labetalol pharmacokinetics in healthy male Chinese subjects.

Purpose: The pharmacokinetics (PK) of labetalol show wide inter-subject variability, but the genetic causes for this are largely undetermined. This study was performed to examine whether common polymorphisms in UGT1A1, UGT2B7, CYP2C19 and ABCB1 affect the PK of labetalol.

Methods: The PK of labetalol were determined in 37 Chinese healthy male subjects who took a single oral dose of 200 mg labetalol.

Impact of CYP2D6 polymorphisms on the pharmacokinetics of lovastatin in Chinese subjects.

Purpose: Although CYP3A4/5 enzymes play the predominant role in the metabolism of simvastatin and lovastatin, polymorphisms in CYP2D6 were reported to be associated with the cholesterol-lowering effect and/or tolerability of simvastatin. This study was performed to examine whether common CYP2D6 polymorphisms affect the pharmacokinetics of lovastatin, which is taken as the inactive prodrug lovastatin lactone and converted to active lovastatin acid.

Methods: A single-dose pharmacokinetic study was performed with lovastatin in 23 Chinese healthy male subjects.

Meclizine metabolism and pharmacokinetics: formulation on its absorption.

Meclizine, an antihistamine, has been widely used for prophylactic treatment and management of motion sickness. However, the onset of action of meclizine was about 1 hour for the treatment of motion sickness and vertigo. A new suspension formulation of meclizine (MOS) was developed with the intention to achieve a rapid effect.