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Objective: E-pharmacies are web sites selling prescription-only medicines and other products including non-prescription and complementary medicines to consumers via the internet. This study aims to evaluate the quality of global e-pharmacies, discuss whether e-pharmacies support the safe and appropriate use of medicines, and consider how we can protect consumers in the future., Methods: A survey of public information published on global e-pharmacy web sites was conducted between July and September 2001. We used a meta-search engine, Copernic, and the search terms of 'online' or 'internet', and 'pharmacy', 'pharmacies' and 'medicines' to identify a sampling frame of global e-pharmacies. We surveyed all web sites in the sampling frame except those under construction or only offering electronic refills, members-only and non-English web sites. Survey data included country of origin, range of medicines sold, prescription requirements, availability of online medical consultations and pharmacists' advice, quality accreditation seals, policies and advertisements., Results: E-pharmacies operated in at least 13 countries; however, the country of origin could not be identified for 22 web sites. Twenty web sites (19%) appeared to supply prescription-only medicines with no prescription required. Only 12% of e-pharmacies displayed quality accreditation seals. We observed information published on e-pharmacy web sites that potentially undermines the safe and appropriate use of medicines., Conclusion: Safeguarding consumers and ensuring the quality of web sites that sell medicines across state and national boundaries is both complex and difficult. Strategies to improve the quality of e-pharmacies include independent third-party regulation of providers, evaluation and enforcement of sanctions in cases of dissemination of fraudulent or harmful information and practices, self-regulation and consumer education. The development of internet regulatory technologies themselves and the resolution of jurisdictional issues offer future solutions but international co-operation is vital.

Objective: The influence of hypoxaemia on the disposition of two common drugs has been examined in ten adults with stable chronic respiratory failure., Methods: There were two experimental periods in this cross-over study: during these periods supplemental oxygen was either withheld or administered to impose clinical hypoxaemia or maintain normoxaemia, respectively. Each participant received either oral (40 mg) or intravenous (20 mg) frusemide combined with oral paracetamol (500 mg) on consecutive days of the two experimental periods., Results: The total (bound plus unbound) plasma clearance of frusemide during hypoxaemia (arterial oxygen tension, PaO2 < or = 50 Torr) was not significantly different from the value during normoxaemia (PaO2 > or = 60 Torr) [76.9 and 62.4 ml.min-1]. The volume of distribution was not affected by acute hypoxaemia (121 ml.kg-1 without and 109 ml.kg-1 with oxygen; P > 0.05). Renal and non-renal clearances of frusemide were similar during the period of hypoxaemia (31 and 38 ml.min-1, respectively) compared to respective values during supplemental oxygen delivery (29 and 32 ml.min-1). The absolute bioavailability of frusemide during hypoxaemia (0.62) was not different to that obtained during normoxaemia (0.56). The combined sodium and potassium excretion rate (expressed as a function of the frusemide excretion rate) was not altered by changing the oxygen tension. The pharmacokinetics of paracetamol were unaffected by hypoxaemia.

Thirteen male patients were administered 20 mg of temazepam orally 1 to 2 h prior to undergoing spinal anaesthesia for a urological procedure. Samples of blood and CSF were drawn just before insertion of the spinal and the concentration of drug estimated in these two media. The results obtained indicated that a highly significant correlation existed between the unbound concentration of temazepam in plasma and the concentration of drug present in CSF. Temazepam appeared to be an effective light pre-medicant in all of the subjects studied.

We have developed a novel and reproducible method for determining the plasma protein binding of the two ibuprofen enantiomers in the presence of each other. The method involves the use of radiolabelled racemic ibuprofen, equilibrium dialysis, derivatization of the enantiomers to diastereomeric amides, high-performance liquid chromatography, and radiochemical analysis. We have determined the plasma protein binding of R(-)- and S(+)-ibuprofen in 6 healthy male volunteers after the oral administration of 800 mg racemic ibuprofen. The mean time-averaged percentage unbound of the R(-)-enantiomer, 0.419 was significantly less than that of the S(+)-enantiomer, 0.643, consistent with stereoselective plasma protein binding. The percentage unbound of each ibuprofen enantiomer was concentration-dependent over the therapeutic concentration range and was influenced by the presence of its optical antipode.

The bioavailability of a rapidly dissolving tablet of theophylline and three brands of standard aminophylline tablets was estimated in a four way cross-over study involving 8 healthy adult volunteers. The relative extent of bioavailability as assessed by the measurement of the total area under the plasma concentration time curves showed no difference between the products (P greater than 0.05). Computed estimates of the rate of drug absorption were similar for all 4 products tested. The results indicate that the rapidly dissolving tablet offers no advantage in respect to rate and extent of absorption over conventional aminophylline tablets.

The pharmacokinetics of a new 10 mg sublingual tablet formulation of temazepam and those of a currently marketed 10 mg oral capsule formulation were evaluated in a group of ten healthy volunteers. No significant differences were observed between the two formulations with respect to any of the pharmacokinetic parameters assessed. Lethargy and somnolence were reported on both capsule and tablet by several subjects at a time which corresponded with the maximum concentration of drug in plasma. The data indicate that the sublingual tablet and orally administered capsule have a similar pharmacokinetic and pharmacodynamic profile.

The pharmacokinetics of theophylline following a single intravenous dose of aminophylline were determined in 8 asthmatic patients in each of the acute, the recovery and the remission phase. The overall results for mean plasma theophylline clearance (78.6 +/- 33.3 ml/kg/h), plasma theophylline half-life (4.14 +/- 1.36 h) and apparent volume of distribution (0.41 +/- 0.066 l/kg) are in accordance with previously published values. There was no general statistically significant difference in any of the pharmacokinetic parameters when results from the acute and remission phases were compared. However, certain patients showed reductions in plasma theophylline clearance in the acute phase of the illness such that a dosage regimen standardised during remission may cause toxicity if continued in the acute episode. It is suggested that monitoring the plasma theophylline levels is desirable in all patients in the acute episode.

We have studied the pharmacokinetics of the anti-mycotic ketoconazole in seven patients who took it for 1-6 months at a dose of 200 mg daily. The mean elimination half-life of the drug was 3.3 h, and although the ketoconazole was given only once daily, a satisfactory clinical response was obtained in all seven individuals. Only a small fraction of the absorbed drug (mean 0.22%) was excreted unchanged in the urine, suggesting almost complete metabolism. Our results support the concept that anti-mycotic activity in the tissues continues after the plasma drug concentration has fallen below a critical level. Our results also support the concept of a change in pharmacokinetics with chronic dosing.