Possible roles of intestinal P-glycoprotein and cytochrome P450 3A on the limited oral absorption of irinotecan.

Objectives: Irinotecan is a widely intravenously used drug for the treatment of certain types of solid tumours. The oral administration of irinotecan has recently been recognized as being a more effective method for the treatment than intravenous administration. However, the limited oral bioavailability of irinotecan poses a problem for its oral delivery.

Tumor Growth Suppression With Novel Intra-arterial Chemotherapy Using Epirubicin-entrapped Water-in-oil-in-water Emulsion .

Background/aim: A mixture of anticancer agents and iodized poppy seed oil (IPSO) has been widely used for intra-arterial chemotherapy of hepatocellular carcinoma. However, the anticancer agents can easily separate from IPSO, so the therapeutic potential is limited. We developed epirubicin-entrapped water-in-oil-in-water emulsion (WOW-Epi) using a double-membrane emulsification technique.

Relationship between UGT1A1*27 and UGT1A1*7 polymorphisms and irinotecan-related toxicities in patients with lung cancer.

Background: The objective of this study was to evaluate the effects of gene polymorphisms, including UGT1A1*7, *27, and *29, on the safety of irinotecan therapy.

Methods: The eligibility criteria were: lung cancer patients scheduled to undergo irinotecan therapy, aged ≥ 20 years, with a performance status of 0-2. Thirty-one patients were enrolled and their blood was collected and used to examine the frequency of UGT1A1*6, *7, *27, *28, and *29 polymorphisms and the concentrations of irinotecan, SN-38, and SN-38G after irinotecan therapy.

Development of the Virtual Physical Assessment Learning Material That Allows the Learners to Check Drug Efficacy and Early Detection of Adverse Effects through Virtual Experience.

 We utilized the information and communication technology to develop the physical assessment (PA) learning materials in the virtual experience type. This learning material consists of two parts which include case learning and basic learning. We created example scenarios about various conditions that a pharmacist may experience in medical scenes such as in a hospital ward, community pharmacy, home, and drugstore.

An advanced objective structured clinical examination using patient simulators to evaluate pharmacy students' skills in physical assessment.

Objective: To implement an advanced objective structured clinical examination (OSCE) in the curriculum and to evaluate Japanese pharmacy students' skills in physical assessment such as measuring pulse and blood pressure, and assessing heart, lung, and intestinal sounds.

Design: An advanced OSCE was implemented in a hospital pharmacy seminar as a compulsory subject. We programmed patient simulators with 21 different patient cases in which normal and abnormal physiological conditions were produced.

Pramipexole reduces parkinsonian tremor induced by pilocarpine infusion in the rat striatum.

Objective: Pramipexole is widely prescribed for the treatment of Parkinson's disease. This dopamine (DA) receptor agonist has a higher affinity for D3 over D2 receptors. We compared the effect of pramipexole to apomorphine, a non-specific DA receptor agonist, on the suppression of tremulous jaw movements (TJMs) in a rat model, to elucidate the possible ameliorating effect of D3 receptor activation on parkinsonian tremor.

Albumin-binding of diclofenac and the effect of a site II inhibitor in the aqueous humor of cataract patients with the instillation of diclofenac.

Diclofenac instillation has been used widely in cataract surgery to prevent postoperative inflammation. Since diclofenac binds strongly to albumin in the circulation, it does not have a sufficient effect on patients in whom diclofenac binds strongly to albumin in the aqueous humor. A decrease in diclofenac binding and an increase in free diclofenac levels are necessary in these patients.

A diclofenac suppository-nabumetone combination therapy for arthritic pain relief and a monitoring method for the diclofenac binding capacity of HSA site II in rheumatoid arthritis.

Diclofenac suppository, a non-steroidal anti-inflammatory drug (NSAID), is used widely in rheumatoid arthritis (RA) patients with severe arthritic pain. As the binding percentage of diclofenac to serum proteins is high, its free (unbound) concentration after rectal administration is low. To increase temporarily the free concentration of diclofenac and to enhance its analgesic effect by inhibiting the protein binding of diclofenac, the analgesic effect of diclofenac was examined before and after the start of an inhibitor administration to RA patients with insufficient control of arthritic pain, and the protein binding capacity of diclofenac was evaluated.

Caffeine increases the antitumor effect of Cisplatin in human hepatocellular carcinoma cells.

Caffeine is thought to increase the antitumor effect of cisplatin or DNA-damaging agents because it is known that caffeine inhibits DNA repair. Caffeine-assisted chemotherapy has been used in the treatment of osteosarcomas. In addition, there are several reports about combination chemotherapy with caffeine for certain malignancies other than osteosarcomas.

Hyuganatsu orange (Citrus tamurana Hort. Ex Tanaka) contains a water soluble substance that suppresses bone loss in ovariectomized rats.

We investigated whether Hyuganatsu orange (Citrus tamurana Hort. ex Tanaka) contains water and acetic-acid soluble substances that increase bone mineral density (BMD) in ovariectomized rats. In in vivo study, femoral BMD can significantly increased.

Hepatocyte growth factor suppresses the anticancer effect of irinotecan by decreasing the level of active metabolite in HepG2 cells.

In the liver, carboxylesterase (CES) converts irinotecan (CPT-11) to its active metabolite SN-38, which exerts anticancer effects. SN-38 is metabolized to an inactive metabolite SN-38 glucuronide by uridine 5'-diphospho-glucuronosyltransferase 1A1 (UGT1A1). Therefore, single nucleotide polymorphisms (SNPs) of the UGT1A1 gene are responsible for the severe adverse effects associated with the disruption of SN-38 metabolism.

Hepatic fibrosis does not affect the pharmacokinetics of 5-fluorouracil in rats.

In the case of cancer chemotherapy for hepatocellular carcinoma, 5-fluorouracil (5-FU) is used widely, and has typically been given by intrahepatic arterial (i.a.) infusion to increase treatment efficacy and to reduce systemic toxicity.

Effect of acute hepatic failure on the hepatic first-pass effect of 5-fluorouracil in rats.

Objectives: In cancer chemotherapy for hepatocellular carcinoma, 5-fluorouracil is widely used and has typically been given by intrahepatic arterial (i.a.) infusion to increase treatment efficacy and reduce systemic toxicity.

Safety, efficacy and pharmacokinetics of S-1 in a hemodialysis patient with advanced gastric cancer.

Purpose: The safety and efficacy of S-1 in hemodialysis patients have not been established. We evaluated the safety and efficacy and pharmacokinetics of S-1 in a hemodialysis patient with advanced gastric cancer.

Patient: A 66-year-old Japanese man with chronic renal failure, who had undergone hemodialysis three times a week for 3 years.

[Medical emergency education using emergency care simulators in the School of Pharmaceutical Sciences].

Clinical pharmacy training III (bedside training) in the School of Pharmaceutical Sciences, Kyushu University of Health and Welfare is intended to train pharmacists who can also cope with medical emergencies. Therefore we produced original scenarios that provide experience of various medical emergencies using emergency care simulators. As a result, these simulators enabled students to experience dealing with various medical emergencies such as cardiopulmonary resuscitation, automated external defibrillation (AED), adrenalin administration, and oxygen inhalation.

Analysis of CYP3A inhibitory components of star fruit (Averrhoa carambola L.) using liquid chromatography-mass spectrometry.

In this study, we analyzed the CYP3A inhibitory components of star fruit Averrhoa carambola L., using liquid chromatography-mass spectrometry (LC-MS). The stereoisomer of procyanidin B1 and B2 and/or the trimer consisting of catechin and/or epicatechin were suggested to be potent inhibitory components.

Effect of acute hepatic failure on epirubicin pharmacokinetics after intrahepatic arterial injection in rats.

In the case of cancer chemotherapy for hepatocellular carcinoma, anthracycline anticancer agents such as epirubicin are widely used, and have typically been given by intrahepatic arterial (i.a.) infusion to increase treatment efficacy and to reduce systemic toxicity.

Inhibitory effects of fruit juices on cytochrome P450 2C9 activity in vitro.

There is limited information on the effect of fruits on human cytochrome P450 (CYP) 2C9 activity. The objective of this study was to determine the effect of fruit juice on CYP2C9-mediated drug metabolism. Nine citrus fruits and eight tropical fruits were chosen.

Dosage plan of a flurbiprofen injection product using inhibition of protein binding by lipid emulsion in rats.

Flurbiprofen-axetil (FP-ax), a bolus injection product of a non-steroidal anti-inflammatory drug (NSAID), is a prodrug of flurbiprofen, an NSAID. As flurbiprofen strongly binds to site II of human serum albumin (HSA), the free (unbound) concentration of flurbiprofen after injection of FP-ax is low. We have examined the inhibitory effect of free fatty acid (FFA), a binding inhibitor for site II of HSA, on the binding of flurbiprofen in-vitro and in-vivo by ultrafiltration, to establish an effective dosage of FP-ax.

Hepatocyte growth factor increases uptake of estradiol 17beta-D-glucuronide and Oatp1 protein level in rat hepatocytes.

Hepatocyte growth factor (HGF) ameliorates liver injuries in hepatectomized cholestatic rats. On the other hand, the protein level of organic anion-transporting polypeptide (Oatp1), which is responsible for the uptake of bile salts into hepatocytes, decreases in cholestatic humans and rats. However, the relationship between the ameliorative effects of HGF and the decrease in Oatp1 levels in cholestasis remains to be understood.

[Need for pharmaceutical skill in using displacement of protein binding].

In pharmacotherapy, to alleviate pains of patients and to provide comforts to patients, pharmacists should improve their pharmaceutical skills of their clinical sense involving pharmaceutical investigational outcomes. Without pharmaceutical skills, pharmacists cannot apply the essence of drug therapies for patients in the most urgent 24 hours treatment. To cope with these drug therapies, we have developed search methods which easily identify the diachronic change of protein binding and the factors in serum (=a new pharmaceutical distribution diagnostic method).

Inhibition of carrier-mediated uptake of epirubicin reduces cytotoxicity in primary culture of rat hepatocytes.

Epirubicin, an antineoplastic drug, is considered to be taken up by tumor cells via a common carrier by facilitated diffusion and is then pumped out in an energy-dependent manner because epirubicin is a substrate for P-glycoprotein (P-gp). However, this study investigated the details of the influx mechanism of epirubicin and demonstrated that epirubicin uptake was mediated by active carrier systems in addition to facilitated diffusion in the primary culture of rat hepatocytes. The uptake of epirubicin gradually increased in a saturated manner when the concentrations were between 1 x 10(-7) M and 1 x 10(-6) M.

[Interpretations of laboratory test data on serum protein binding].

Serum proteins that are important in the serum protein binding of drugs are human serum albumin (HSA) and alpha1-acid glycoprotein (AGP). Several binding sites exist on HSA and AGP molecules. HSA, AGP, free fatty acid (FFA), blood urea nitrogen (BUN) and bilirubin, which can all be determined by laboratory test, affect the binding capacities of binding sites on these proteins.

Effects of pomegranate juice on human cytochrome P450 2C9 and tolbutamide pharmacokinetics in rats.

In this study, we investigated whether pomegranate juice could inhibit CYP2C9 activity. The ability of pomegranate juice to inhibit the diclofenac 4'-hydroxylase activity of human CYP2C9 was examined using human liver microsomes. Pomegranate juice was shown to be a potent inhibitor of human CYP2C9.

Isolation of cytochrome P450 3A (CYP3A) inhibitors from Hyuganatsu, Citrus tamurana Hort.

The present study was conducted to identify cytochrome P450 3A (CYP3A) inhibitory components of Hyuganatsu, Citrus tamurana Hort., by investigating the effects on midazolam 1'-hydroxylase activity of human liver microsomes. As a consequence, limonin and nomilin were identified as CYP3A inhibitors from the endocarp of Hyuganatsu.