Prescription drug samples: Does this marketing strategy counteract policies for quality use of medicines?

Prescription drug samples, as used by the pharmaceutical industry to market their products, are of current interest because of their influence on prescribing, and their potential impact on consumer safety. Very little research has been conducted into the use and misuse of prescription drug samples, and the influence of samples on health policies designed to improve the rational use of medicines. This is a topical issue in the prescription drug debate, with increasing costs and increasing concerns about optimizing use of medicines. This manuscript critically evaluates the research that has been conducted to date about prescription drug samples, discusses the issues raised in the context of traditional marketing theory, and suggests possible alternatives for the future.

A convergent solution-phase synthesis of the macrocycle Ac-Phe-[Orn-Pro-D-Cha-Trp-Arg], a potent new antiinflammatory drug

Relatively few cyclic peptides have reached the pharmaceutical marketplace during the past decade, most produced through fermentation rather than made synthetically. Generally, this class of compounds is synthesized for research purposes on milligram scales by solid-phase methods, but if the potential of macrocyclic peptidomimetics is to be realized, low-cost larger scale solution-phase syntheses need to be devised and optimized to provide sufficient quantities for preclinical, clinical, and commercial uses. Here, we describe a cheap, medium-scale, solution-phase synthesis of the first reported highly potent, selective, and orally active antagonist of the human C5a receptor. This compound, Ac-Phe[Orn-Pro-D-Cha-Trp-Arg], known as 3D53, is a macrocyclic peptidomimetic of the human plasma protein C5a and displays excellent antiinflammatory activity in numerous animal models of human disease. In a convergent approach, two tripeptide fragments Ac-Phe-Orn-(Boc)-Pro-OH and H-D-Cha-Trp(For)-Arg-OEt were first prepared by high-yielding solution-phase couplings using a mixed anhydride method before coupling them to give a linear hexapeptide which, after deprotection, was obtained in 38% overall yield from the commercially available amino acids. Cyclization in solution using BOP reagent gave the antagonist in 33% yield (13% overall) after HPLC purification. Significant features of the synthesis were that the Arg side chain was left unprotected throughout, the component Boe-D-Cha-OH was obtained very efficiently via hydrogenation Of D-Phe with PtO2 in TFA/water, the tripeptides were coupled at the Pro-Cha junction to minimize racemization via the oxazolone pathway, and the entire synthesis was carried out without purification of any intermediates. The target cyclic product was purified (>97%) by reversed-phase HPLC. This convergent synthesis with minimal use of protecting groups allowed batches of 50100 g to be prepared efficiently in high yield using standard laboratory equipment. This type of procedure should be useful for making even larger quantities of this and other macrocyclic peptidomimetic drugs.

Pilot study to determine the ability of health-care professionals to undertake drug dose calculations

Background: It is essential for health-care professionals to calculate drug doses accurately. Previous studies have demonstrated that many hospital doctors were unable to accurately convert dilutions (e.g. 1:1000) or percentages (e.g. percentage w/v) of drug concentrations into mass concentrations (e.g. mg/mL). Aims: The aims of the present study were to evaluate the ability of health-care professionals to perform drug dose calculations accurately and to determine their preferred concentration convention when calculating drug doses. Methods: A selection of nurses, medical students, house surgeons, registrars and pharmacists undertook a written survey to assess their ability to perform five drug dose calculations. Participants were also asked which concentration convention they preferred when calculating drug doses. The surveys were marked then analysed for health-care professionals as a whole and then by subgroup analysis to assess the performance of each health-care-professional group. Results: Overall, less than 14% of the surveyed health-care professionals could answer all five questions correctly. Subgroup analysis revealed that health-care pro-fessionals' ability to calculate drug doses were ranked in the following order: registrars approximate to pharmacists > house surgeons > medical students >> nurses. Ninety per cent of health-care professionals preferred to calculate drug doses using the mass concentration convention. Conclusions: Overall, drug dose calculations were performed poorly. Mass concentration was clearly indicated as the preferred convention for calculating drug doses.

Which drug combination for hormone-refractory prostate cancer

Patients with metastatic hormone-refractory prostate cancer have a progressive disease with a median survival of similar to 11 months, and currently no treatment offers a survival advantage. The standard drug treatment is a corticosteroid and chemotherapy with mitoxantrone. In a comparison of docetaxel every 3 weeks and prednisone, versus mitoxantrone and prednisone, with a follow-up of similar to 21 months, there were less deaths in the docetaxel group than in the mitoxantrone group (166 of 335 patients and 201 of 337 patients, respectively). Docetaxel also prolonged the duration of survival compared with mitoxantrone (18.9 and 16.5 months, respectively). When given with prednisone, docetaxel was also shown to reduce pain and serum prostate specific antigen levels and improve quality of life compared with mitoxantrone/prednisone. In another trial in hormone-resistant prostate cancer patients, which compared docetaxel and estramustine with mitoxantrone and prednisone during a median follow-up of 32 months, there were fewer deaths with docetaxel/estramustine than with mitoxantrone/prednisone, which were 217 of 338 and 235 of 336 patients, respectively. Median survival was also longer in the docetaxel and estramustine group than in the mitoxantrone/prednisone group (17.5 and 15.6 months, respectively). In conclusion, two combinations (docetaxel/prednisone and docetaxel/estramustine) have been shown to be superior to mitoxantrone/prednisone in hormone-refractory prostate cancer and both should be considered for use. With the present information, there is little to distinguish between these combinations.