Terms Of Patient Compliance Research Articles

Bioavailability of metoclopramide from a new chewing gum device

Metoclopramide is widely used in the treatment of nausea. The development of metoclopramide as medicated chewing gum has potential advantages in terms of patient compliance, fast onset of effect and improved bioavailability. In this study, bioavailability of metoclopramide from a new chewing gum device, 3TabGum, was evaluated in healthy volunteers. Medicated chewing gum was well tolerated in all subjects. Compared with immediate release tablets, AUC following administration of chewing gum was higher (224.9 vs. 166.5ngh/mL), while tmax was smaller (1.38 vs. 1.88h), suggesting improved bioavailability and rapid onset of drug absorption. However, absorption rate was lower, as evidenced by lower Cmax (17.2 vs. 20.8ng/mL). Terminal half-life was prolonged (11.58 vs. 5.35h), implying that initial fast release of metoclopramide is followed by much slower release of the remaining smaller portion of the drug. These results indicate that chewing gum is a promising alternative to current metoclopramide formulations.

Knee versus Thigh Length Graduated Compression Stockings for Prevention of Deep Venous Thrombosis: A Systematic Review

Objective Graduated compression stockings are a valuable means of thrombo-prophylaxis but it is unclear whether knee-length (KL) or thigh length (TL) stockings are more effective. The aim of this review was to systematically analyse randomised controlled trials that have evaluated stocking length and efficacy of thromboprophylaxis. Method A systematic review of the literature was undertaken. Clinical trials on hospitalised populations and passengers on long haul flights were selected according to specific criteria and analysed to generate summated data. Results 14 randomized control trials were analysed. Thirty six of 1568 (2.3%) participants randomised to KL stockings developed a deep venous thrombosis, compared with 79 of 1696 (5%) in the TL control/thigh length group. Substantial heterogeneity was observed amongst trials. KL stockings had a significant effect to reduce the incidence of DVT in long haul flight passengers, odds ration 0.08 (95%CI 0.03–0.22). In hospitalised patients KL stockings did not appear to be far worse than TL stockings, odds ratio 1.01 (95%CI 0.35–2.90). For combined passengers and patients, there was a benefit in favour of KL stockings, weighted odds ratio 0.45 (95% CI 0.30–0.68). Conclusion KL graduated stockings can be as effective as TL stockings for the prevention of DVT, whilst offering advantages in terms of patient compliance and cost.

Prospects for the Development of Long-Acting Formulations of Human Somatropin

In healthy humans, growth hormone (GH) is secreted in distinct pulses with an underlying nyctohemeral pattern. Current forms of somatropin replacement are unable to closely mimic such a release pattern, but are still able to exert the beneficial action of GH. A limited number of short-term studies in rodents and humans suggest that longitudinal growth may be superior when somatropin is given with a pulsatile mode of administration, whereas hepatic insulin-like growth factor-I generation and beneficial changes in body composition appear to be equal or even enhanced with continuous somatropin administration.Recent developments in drug delivery technology have allowed the use of slow-release preparations of somatropin in humans. The most successful technology so far has been the encapsulation of somatropin molecules in poly(D,L-lactic-co-glycolic acid) biodegradable microspheres. Pharmacokinetic and pharmacodynamic data have been published on two such preparations; Nutropin Depot((R)) and hGH-Biosphere((R)). The latter has a superior release profile, but outcomes data from multicenter trials in both children and adults have been presented for the former: catch-up growth was observed in children, although to a lesser degree than historic comparative data obtained with the use of daily somatropin injections and the effects on metabolic derangements in GH-deficient patients appeared similar to those observed with daily injections. Improved sustained-release somatropin preparations will need further study of their long-term efficacy, but, if successful, will be highly attractive in terms of patient compliance and convenience.

HPTLC procedure for determination of levonorgestrel in the drug-release media of an in-situ-forming delivery system

Levonorgestrel, 13β-ethyl-17β-hydroxy-18,19-dinor-17α-pregn4-en-20-yn-3-one (Figure 1), is a safe, potent, synthetic steroidal hormone that is widely used in several contraceptive delivery systems [1, 2], for example oral contraceptives and injectable [3], implantable [4, 5], and intrauterine devices [6]. Evolution of an existing drug molecule from a conventional form to a polymeric novel delivery system can significantly improve its performance in terms of patient compliance, safety, and efficacy. Among these polymeric systems, biodegradable in-situ-forming drug-delivery systems have received considerable attention over the past few years [7–9]. Dunn et al. [10] introduced an in-vivo setting system, made from biodegradable polymers, for human and veterinary purposes. This injectable implant system comprises a water-insoluble biodegradable polymer, for example poly (DL-lactide-co-glycolide), dissolved in a water-miscible, physiologically compatible organic solvent, for example N-methyl-2-pyrrolidone. On injection into an aqueous environment, the organic solvent diffuses into the surrounding environment while water diffuses into the polymer matrix. The polymer precipitates on contact with the water and results in a solid polymeric implant.

Budesonide once versus twice‐daily administration: meta‐analysis

The aim of this study was to examine the efficacy of budesonide administered once daily compared to twice daily in asthma. Meta-analysis of randomised controlled trials comparing budesonide administered once versus twice a day that presented data on at least one clinical outcome measure was conducted. A total of 10 studies, with 1922 children and adults with asthma, met the inclusion criteria. These studies were performed predominantly with mild to moderate asthmatic patients, using doses of budesonide ranging from 200 to 800 microg per day. There was no significant difference between daily dosing once or twice for all the clinical outcome variables, including withdrawals due to asthma, for which the odds ratio was 1.0 (95% confidence interval, 0.65-1.52). In mild to moderate asthma a once-daily budesonide regimen has a similar efficacy to a twice-daily regimen in doses up to 800 microg per day. A once-daily regimen has potential advantages in terms of patient compliance and satisfaction, when used in clinical practice.

Transdermal iontophoretic delivery of methylphenidate HCl in vitro

Methylphenidate is prescribed orally for Attention Deficit Disorder in children and adults, and for narcolepsy patients. Methylphenidate has a short plasma half-life (1–2 h) and thus needs to be frequently administered for effective therapy. Such therapy has limitations in terms of patient compliance, particularly in young children. For such reasons, the development of a transdermal dosage form of methylphenidate may be useful. This study was undertaken to evaluate the passive and electrically assisted transport (iontophoresis) of methylphenidate from aqueous methylphenidate hydrochloride solutions across excised human skin. A maximum flux of 12.0 μg/(cm 2 h) of protonated methylphenidate was estimated from the passive transport data at pH 3.5. Iontophoresis significantly enhanced protonated methylphenidate transport as compared with passive delivery. From the present experiments, the efficiency of iontophoretic delivery of methylphenidate was approximately 700 μg/(mA h). Based on in vitro skin flux data, the daily dose of 15–40 mg methylphenidate can be achieved using a current density of 0.5 mA/cm 2 and a minimum transport area of 2–5 cm 2 for 24-h application, or an area of 4–10 cm 2 for 12-h (daytime) application. From methylphenidate skin flux values, methylphenidate mobility of 2.2×10 −4 cm 2/(V s) was estimated, which compares reasonably with its free solution mobility of 6.6×10 −4 cm 2/(V s).

Vaginal delivery after two or more previous caesarean sections: is trial of labour contraindicated?

A retrospective study was conducted involving 308 patients with previous caesarean sections and current singleton pregnancy. All the women delivered at the University Teaching Hospital Zaria, after having been in established labour. The aim was to determine any significant maternal and fetal risk attributable to labour in patients with more than one previous caesarean which may mitigate against a trial of vaginal delivery. The study analysis involved a group of patients with one previous caesarean section compared with those with more than one (multiple) caesarean section who delivered vaginally or abdominally after having been in established labour. The results showed that there was no significant difference in maternal and perinatal mortality rates and perinatal morbidity rates between the two groups. The patients with multiple caesarean sections who failed to deliver vaginally had increased rates of postoperative pyrexia (18.7%), anaemia (23.4%) and blood transfusion (35.3%). The study showed that the risk of fatal outcome related to labour in patients with multiple caesarean sections was low and could be eliminated by careful patient selection and close intrapartum care. A positive review of policy towards a trial of vaginal delivery in multiple caesarean sections is therefore advocated in view of the advances in patient management in contemporary obstetric care. The gains in terms of patient compliance towards hospital care and supervised delivery will be considerable. A multicentre, prospective case-controlled trial will clearly define the risks attributable to this policy change.

Felodipine (once daily) versus nifedipine (four times daily) for Prinzmetal's angina pectoris

In 30 consecutive patients with Prinzmetal's angina pectoris, the antiischemic effect of felodipine, a new long-acting vasoselective calcium antagonist, administered at doses of 10 and 20 mg once daily was compared with that of the wellestablished therapeutic regimen with nifedipine administered at a dose of 20 mg 4 times daily. Twenty-four-hour Holter monitoring was performed during a 2-day placebo run-in and at the end of each of 3 consecutive 6-day periods during which the 3 active treatments were administered in randomized sequence. Three patients withdrew, whereas 27 completed the study. The therapeutic regimens tested proved to be similarly effective; primary end points (ischemic episodes recorded by Holter monitoring, and anginal attacks reported on diary cards) occurred in 5 patients (19%) during nifedipine treatment, and in 7 (26%) and 3 (11%) during felodipine treatment with 10 and 20 mg, respectively (p = not significant). The distribution of residual ischemic episodes demonstrated that treatment with felodipine once daily provides 24-hour antiischemic protection. Twenty-six patients were followed up with 20 mg of felodipine once daily for a mean of 6 ± 5 months, and 21 of them (81%) remained free of symptoms and Holter-recorded ischemic attacks. It is concluded that for Prinzmetal's angina pectoris, 24-hour antiischemic protection may be achieved with administration of felodipine once daily. The availability of a simplified therapeutic approach may constitute a real advantage in terms of patient compliance and improving the quality of life.

Can clinical trials in rheumatology be improved?

With our growing dependence on clinical trials to assess the adequacy of available treatments for arthritic patients, attention is increasingly being focused on the tools we use in the design, analysis, and reporting of these studies and the ways in which we can improve them. This review outlines some of the major problems in terms of patient compliance, trial size, inadequate endpoints, and insufficient reporting, and highlights some of the work being done to overcome these difficulties. The greatest emphasis is placed on two issues. Firstly, there is a need for greater stringency in interpreting the results. Thus, more consideration needs to be devoted to the limitations of the measurements used and greater emphasis needs to be placed on analysis on the basis of "intention to treat". Secondly, there is a need to standardize common aspects of the trials, such as the detailed reporting of baseline data, a minimal set of outcome measures, comparable response thresholds, and the inclusion of statistics such as confidence intervals. Implementing these changes will increase comparability and yield a stronger possibility of significant results.