Gabapentin is approved for the treatment of postherpetic neuralgia (PHN) and epilepsy. The pharmacokinetic (PK) properties of gabapentin, including absorption, distribution, metabolism, and excretion (ADME), were investigated during the development of Neurontin®, an immediate-release (IR) formulation of gabapentin that is orally administered three-times daily. Recently, a gastroretentive (GR) once-daily formulation of gabapentin (Gralise®) has been developed and marketed for the treatment of PHN. This review focuses on the ADME properties of gabapentin and illustrates how GR delivery enhances its absorption compared with IR formulations and allows once-daily dosing with the evening meal for the treatment of PHN. It includes the following aspects: 1) the mechanism of gastroretention of gabapentin GR tablets, 2) in vitro dissolution profiles of the GR and IR formulations, 3) site of absorption of gabapentin in the human intestine, 4) studies of the mechanism of gabapentin absorption using intestinal tissue preparations, 5) human PK studies to examine the effects of dose and formulations on PK profiles and the bioavailability of gabapentin at therapeutically relevant doses, and 6) efficacy and safety of gastroretentive gabapentin in patients with PHN. The data reviewed support that GR delivery of gabapentin optimizes its absorption via a saturable uptake mechanism. The prolonged residence of the GR tablets in the stomach coupled with the gradual release of gabapentin attenuates saturation of the transporter, thus enhancing absorption and increasing bioavailability, especially at therapeutically relevant doses. The net result is a once-daily formulation of gabapentin that is well tolerated and efficacious for the treatment of PHN.
Objective
To investigate the level and influencing factors of nursing postgraduate student′s career expectation, and supply scientific reference for career planning of them.
Methods
From October 2014 to February 2015, a total of 110 nursing postgraduate students in 12 universities from Shanghai, Beijing, Jiangsu, Zhejiang and Shanxi provinces were tested by the Chinese version of Career Expectations Scale.
Results
The average score of their career expectation was (3.844±0.614), and the highest score was the extrinsic value dimension (4.029±0.726) comparing with the lowest score the prestige status and stability dimension (3.584±0.670). Multiple linear regression analysis showed that interest in the nursing profession was the influencing factors of the student′s career expectation.
Conclusions
Nursing postgraduate student′s career expectation needs to be further improved. Nursing educators and managers should pay more attention to career planning of nursing master specialist, and develop strategies to adjust the level of their career expectation, to improve the development of professional career.
Key words:
Nursing; Education, postgraduate student; Professional degree; Career Expectation
We generated the organic anion transporting polypeptide (Oatp) 1b2 knockout (KO) mouse model and assessed its utility to study hepatic uptake using model compounds: cerivastatin, lovastatin acid, pravastatin, simvastatin acid, rifampicin, and rifamycin SV. A selective panel of liver cytochromes P450 (P450s) (Cyp3a11, Cyp3a13, Cyp3a16, Cyp2c29, and Cyp2c39) and transporters [Oatp1b2, Oatp1a1, Oatp1a4, Oatp1a5; organic anion transporter (Oat) 1, Oat2, Oat3; multidrug resistance gene 1 (Mdr1) a, Mdr1b; bile salt export pump, multidrug resistance associated protein (Mrp) 2, Mrp3; breast cancer resistance protein] were measured by reverse transcription-polymerase chain reaction in both KO and wild-type (WT) male mice. Male KO and WT mice received each model compound s.c. at 3 mg/kg. Blood and liver samples were obtained at 0, 0.5, and 2 h postdose and analyzed using liquid chromatography/tandem mass spectrometry. Liver/plasma concentration ratio (Kp,liver) was calculated. Student9s t test was used to compare the mRNA and Kp,liver between the KO and WT mice. A similar mRNA expression was observed between the KO and WT for the selected P450s and transporters except for Oatp1b2, for which the level was negligible in the KO but prominent in the WT mice with P < 0.0001. The in vivo results showed a differential effect of Oatp1b2 on hepatic uptake of the model compounds, indicating that Oatp1b2 plays a more significant role in the hepatobiliary disposition of rifampicin and lovastatin than the other compounds tested. This study suggests the Oatp1b2 mouse as a useful in vivo tool to understand drug targeting and disposition in the liver.
Background: This study aimed to examine the preliminary reliability and validity of a Chinese version of the Ward Organizational Features Scales (C-WOFS).
Methods: An existing English version of the WOFS was adapted. Translation and back-translation were conducted to ensure linguistic consistency and cultural sensitiveness. The C-WOFS comprises six scales including the Scales of Physical Environment of the Ward, Professional Nursing Practice, Professional Working Relationships, Ward Leadership, Nurses’ Influence, and Job Satisfaction. Then a crosssectional survey was conducted, and 1200 nurses were recruited from four general hospitals in two districts of Shanghai, China. 994 of them completed the survey.
Results: Confirmatory factor analysis of the six originally-specified scales indicated a poor fit to the data. A subsequent Exploratory Factor Analysis (EFA) improved the fit. After EFA, all items in the Scale of Physical Environment of the Ward were retained, and 16 items were removed from the other five scales. Two factors were generated from the original version of one-domain Job Satisfactory Scale, while the domains of the other five scales were the same as those in the original scales. The final version of C-WOFS contained 88 items and 15 subscales, distributed across six scales. The Cronbach’s α for each scale and subscale ranged from 0.71 to 0.94.
Conclusion: The preliminary reliability and validity of the C-WOFS is satisfactory and promising to assess and correlate ward organizational features of hospitals in Mainland China. Further psychometric properties of the C-WOFS will be tested and reported.
Since the generation of the multi-drug resistance 1 (mdr1) gene knockout (KO) mice in the early 90 s, these animals have been instrumental to our understanding of the physiological roles of mdr1 gene product P-glycoprotein. Located in crucial organs such as brain, intestine, liver, and kidney, P-glycoprotein-mediated transport has been shown to affect both the pharmacokinetics and pharmacodynamics of endogenous compounds and xenobiotics. It appears that P-glycoprotein may not be essential for the maintenance of normal body function as suggested by the similarity in life span and serum chemistry values of mdr1 gene KO mice compared to their genetically competent littermates. However, numerous studies have demonstrated that P-glycoprotein limits the brain penetration of many drug substrates. The reduced central nervous system (CNS) access of these compounds has been linked to decreased pharmacological or toxicological effects. In contrast to the critical role that P-glycoprotein plays in the brain, the extent of P-glycoprotein involvement in oral absorption and hepatobiliary or renal excretion of xenobiotics appears more variable. In addition to the mdr1 gene KO model, in vitro cell lines that over-express P-glycoprotein, and clinical trials using P-glycoprotein modulators have allowed for the comparison of in vitro-in vivo and species related difference in P-glycoprotein activity. For the most part, studies have shown reasonable in vitro-in vivo correlations, modest species-related differences, and comparable human-mouse in vivo P-glycoprotein effects on systemic drug disposition. Therefore, the mdr1 gene KO mouse model, when used appropriately, may allow for prediction of CNS drug access and certain drug-drug interaction.
148 Background: Fentanyl pectin nasal spray(FPNS) contains fentanyl citrate and is approved for treatment of breakthrough cancer pain. Nasal delivery allows direct nasal epithelium-to-blood absorption of fentanyl, and thus rapid and effective pain relief. This study evaluated the effect of dosing interval on pharmacokinetics (PK) and safety/tolerability of FPNS. Methods: This was an open-label randomized study in healthy volunteers. Five treatments were administered under naltrexone block to the right nostril, with a ≥3-day washout period: 1 x 100 μg (A); 2 x 100 μg, 4-hr (B), 2-hr (C), and 1-hr apart (D); and 8 x 100 μg consecutively (E). Blood samples were collected and analyzed for plasma fentanyl concentrations. PK data were derived using a non-compartmental model method. Results: 13 subjects were enrolled, 10 (77%) completed the study. For the two-dose regimens, C max was higher after the second dose than the first; the increase was statistically significant for the 1- and 2-hr intervals, but not the 4-hr. There were no significant differences in AUC among them. Eight consecutive 100-µg doses resulted in an ~5-fold in C max and AUC of those of a single 100-µg dose, suggesting a less than dose proportional increase in rate (peak) and extent (AUC). No new adverse events (AEs) were observed. 53% of subjects reported ≥1 AE, with dizziness (11.9%) and somnolence (4.9%) most common. 12.9% of subjects discontinued due to AEs. All AEs rapidly decreased to sustained low levels after 4–5 weeks. Conclusions: FPNS at 100-800 µg was well tolerated. The shorter the dosing interval, the higher the second C max . Dosing interval had no effect on AUC. Exposure plateaued after 8 consecutive 100 µg doses to the same nostril, suggesting an additional safety feature of FPNS. [Table: see text]
Trust is advocated as the single most important factor for consumers choosing an online supplier. To study trust mechanisms underlying consumer-e-retailer exchange relationship, this research takes a new perspective, a perspective directed toward customer retention. By bringing together three diverse approaches–trust literature, global evaluations theory, and transaction costs analysis, this study develops an integrative model of consumer trust in an e-retailer. Data for the study was collected using an online survey distributed via email to a national sample of 4,156 online consumers who were randomly drawn from a panel containing about 3 million people. Hypotheses were tested using structural equation modeling, multiple regression analysis, and multiple group analysis. Findings of the study imply that consumer trust in an e-retailer derives not only from a consumer’s web experience but also from his/her experience outside the web. Specifically, a consumer’s attitudes toward the key components of his/her entire online purchase experience (i.e., website design, fulfillment/reliability, privacy/security, and customer service) constitute the key drivers of consumer trust. Findings also indicate that trust is intrinsically beneficial. If a consumer trusts an e-retailer, he/she will come back in the future or even become loyal to the e-retailer. Further, findings suggest that though trust has a direct effect on future intentions and loyalty, part of its effect is conditional on its ability to reduce transaction costs. Additionally, findings of the study imply that as contextual factors, consumer dependence on an e-retailer confounds the effects of trust on future intentions and loyalty, and uncertainty surrounding online transacting environments moderates the effect of trust on future intentions. However, environmental uncertainty was not found to confound the effect of trust on loyalty. Finally, findings suggest that trust mechanisms underlying consumer-multi-channel e-retailer exchange relationship might be different from those underlying consumer -pure e-retailer relationship. Future research into this area is warranted.
The pharmacokinetics (PKs) of sodium oxybate (SXB) was evaluated in a subset of participants from a study of SXB treatment in children (aged 7-11 years; n = 11) and adolescents (aged 12-17 years; n = 18) with narcolepsy with cataplexy. PK evaluation was conducted over 2 nights during the period when participants received a stable nightly SXB dose. The SXB dose on night 1 was half of night 2 and was administered in two equally divided doses: dose 1 was administered > 2 hours after the evening meal, and dose 2 was administered ≥ 4 hours after dose 1. Noncompartmental PK analysis demonstrated higher plasma concentrations post-dose 2 vs. post-dose 1, higher than dose-proportional increases in area under the concentration-time curve from 0 to 4 hours (AUC0-4h ) after dose 1, indicating nonlinear clearance, and better correlation between exposure and mg/kg than exposure and gram dose. To confirm the noncompartmental findings, identify factors affecting SXB PK, and compare with prior results in adults, a population PK (PopPK) model was established combining PK data from the current study with prior data from adults (132 healthy volunteers and 13 with narcolepsy). A two-compartment PopPK model with first-order absorption and nonlinear clearance from the central compartment described the data well. PopPK identified weight as the main intrinsic factor and food as the main extrinsic factor affecting SXB PK, and predicts similar PK profiles on a mg/kg basis across ages. These results, along with previously reported efficacy and safety outcomes, support weight-based SXB dose initiation in pediatric patients.
Objective
To evaluate the professional practice abilities of emergency and intensive care nurses from 5 hospitals at Kashi region of Xinjiang through objective structured clinical examination(OSCE), in order to provide an effective intervention strategies to improve the professional practice abilities of nurses.
Methods
A total of 37 emergency and intensive care nurses from5 hospitalsin Kashiwere examined regarding the professional practice abilities in nursing assessment, nursing plan, nursing implementation and nursing effects evaluation by OSCE.
Results
The overall score of OSCE was (110.13±28.15)which wasa medium level (total 200 points), among which, nursing assessment score was (35.66±8.54) with a highest percentage with full credits; nursing plan score was (19.79±6.09) with a lowest percentage out of full credits; nursing implementation score was (43.35±15.92) and nursing effects evaluation score was (11.32±3.94). There are statistical differences of OSCE among emergency and intensive care nurses with different hospitals, professionaltitles, educational backgrounds and length of working(P<0.05).
Conclusions
Professional practice abilities of emergency and intensive care nurses need to be further improved at Kashi region of Xinjiang, which can be achievedthrough enhancing targeted training for nurses with low education and seniority in regional hospitals, and upgrading the training and examination methodto improve the ability of professional practice.
Key words:
Emergency and intensive care nurse; Professional practice ability; Objective structured clinical examination
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