Veterinary drug delivery: Potential for skin penetration enhancement

A range of topical products are used in veterinary medicine. The efficacy of many of these products has been enhanced by the addition of penetration enhancers. Evolution has led to not only a highly specialized skin in animals and humans, but also one whose anatomical structure and skin permeability differ between the various species. The skin provides an excellent barrier against the ingress of environmental contaminants, toxins, and microorganisms while performing a homeostatic role to permit terrestrial life. Over the past few years, major advances have been made in the field of transdermal drug delivery. An increasing number of drugs are being added to the list of therapeutic agents that can be delivered via the skin to the systemic circulation where clinically effective concentrations are reached. The therapeutic benefits of topically applied veterinary products is achieved in spite of the inherent protective functions of the stratum corneum (SQ, one of which is to exclude foreign substances from entering the body. Much of the recent success in this field is attributable to the rapidly expanding knowledge of the SC barrier structure and function. The bilayer domains of the intercellular lipid matrices within the SC form an excellent penetration barrier, which must be breached if poorly penetrating drugs are to be administered at an appropriate rate. One generalized approach to overcoming the barrier properties of the skin for drugs and biomolecules is the incorporation of suitable vehicles or other chemical compounds into a transdermal delivery system. Indeed, the incorporation of such compounds has become more prevalent and is a growing trend in transdermal drug delivery. Substances that help promote drug diffusion through the SC and epidermis are referred to as penetration enhancers, accelerants, adjuvants, or sorption promoters. It is interesting to note that many pour-on and spot-on formulations used in veterinary medicine contain inert ingredients (e.g., alcohols, amides, ethers, glycols, and hydrocarbon oils) that will act as penetration enhancers. These substances have the potential to reduce the capacity for drug binding and interact with some components of the skin, thereby improving drug transport. However, their inclusion in veterinary products with a high-absorbed dose may result in adverse dermatological reactions (e.g., toxicological irritations) and concerns about tissue residues. These a-re important considerations when formulating a veterinary transdermal product when such compounds ate added, either intentionally or otherwise, for their penetration enhancement ability. (C) 2001 Elsevier Science B.V. All rights reserved.

Matching prescription claims with medication data for nursing home residents: Implications for prescriber feedback, drug utilisation studies and selection of prescription claims database

Medication data retrieved from Australian Repatriation Pharmaceutical Benefits Scheme (RPBS) claims for 44 veterans residing in nursing homes and Pharmaceutical Benefits Scheme (PBS) claims for 898 nursing home residents were compared with medication data from nursing home records to determine the optimal time interval for retrieving claims data and its validity. Optimal matching was achieved using 12 weeks of RPBS claims data, with 60% of medications in the RPBS claims located in nursing home administration records, and 78% of medications administered to nursing home residents identified in RPBS claims. In comparison, 48% of medications administered to nursing home residents could be found in 12 weeks of PBS data, and 56% of medications present in PBS claims could be matched with nursing home administration records. RPBS claims data was superior to PBS, due to the larger number of scheduled items available to veterans and the veteran's file number, which acts as a unique identifier. These findings should be taken into account when using prescription claims data for medication histories, prescriber feedback, drug utilisation, intervention or epidemiological studies. (C) 2001 Elsevier Science Inc. All rights reserved.

Increasing relevance of pharmacogenetics of drug metabolism in clinical practice

Much of the individual variation in drug response is due to genetic drug metabolic polymorphisms. Clinically relevant examples include acetylator status; cytochrome P450 2D6, 2C9 and 2C19 polymorphisms; and thiopurine methyltransferase deficiency. It is important to be aware of which drugs are subject to pharmacogenetic variability. In the future, population-based pharmacogenetic testing will allow more individualized drug treatment and will avoid the current empiricism.

Novel colloidal materials for high-throughput screening applications in drug discovery and genomics

Tracking the reaction history is the means of choice to identify bioactive compounds in large combinatorial libraries. The authors describe two approaches to synthesis on silica beads: a) addition of a reporter dye tag during each synthesis step (see Figure), which attaches itself to the bead by colloidal forces, and b) encapsulating arrays of fluorescent dyes into the beads to encode them uniquely, for recognition with a flow cytometer after each reaction step.

Drug use evaluation of ipratropium bromide at two tertiary referral hospitals in Brisbane.

Objective: To assess the appropriateness of ipratropium bromide prescribing in two tertiary referral hospitals. Method: Criteria for optimal use were developed based on current literature and modified after consultation with respiratory physicians and clinical pharmacists. A prospective review of prescribing was performed over a 2-month period to assess conformity to these criteria. Results: Information was collected from 84 patients; 5% were receiving inhalers and 96% nebuliser therapy (one patient used both). 77% of patients (n = 65) had a principal diagnosis of chronic obstructive pulmonary disease, 14% (n = 12) asthma and 8% (n = 7) had neither diagnosis. 75% of patients were using ipratropium outside the guidelines. The major areas where the guidelines were not met were a lack of therapeutic justification, use of inappropriate doses, and use of an inappropriate delivery device. Feedback and educational interventions were designed and delivered based on the data obtained. Conclusions: There was widespread use of ipratropium outside the developed guidelines. Interventions in specific areas could lead to significant improvements in the use of this high cost drug

Clinically significant drug interactions with agents specific for migraine attacks

The drugs which provide specific relief from migraine attacks, the ergopeptides (ergotamine and dihydroergotamine) and the various 'triptans' (notably sumatriptan), are often prescribed for persons already taking various migraine preventative agents, and sometimes drugs for other indications. As a result, migraine-specific drugs may become involved in drug-drug interactions. The migraine-specific drugs all act as agonists at certain subclasses of serotonin (5-hydroxytryptamine; 5-MT) receptor, particularly those of the 5-HT1D subtype, and produce vasoconstriction through these receptor-mediated mechanisms. The oral bioavailabilities of these drugs, particularly those of the ergopeptides, are often incomplete, due to extensive presystemic metabolism. As a result, if migraine-specific agents are coadministered with drugs with vasoconstrictive properties, or with drugs which inhibit the metabolism of the migraine-specific agents, there is a risk of interactions occurring which produce manifestations of excessive vasoconstriction. This can also occur through pharmacodynamic mechanisms, as when ergopeptides or triptans are coadministered with methysergide or propranolol (although a pharmacokinetic element may apply in relation to the latter interaction), or if one migraine-specific agent is used shortly after another. When egopeptide metabolism is inhibited by the presence of macrolide antibacterials, particularly troleandomycin and erythromycin, the resultant interaction can produce ergotism, sometimes leading to gangrene. Similar pharmacokinetic mechanisms, with their vasoconstrictive consequences, probably apply to combination of the ergopeptides with HIV protease inhibitors (indinavir and ritonavir), heparin, cyclosporin or tacrolimus. Inhibition of triptan metabolism by monoamine oxidase A inhibitors, e.g. moclobemide, may raise circulating triptan concentrations, although this does not yet seem to have led to reported clinical problems. Caffeine may cause increased plasma ergotamine concentrations through an as yet inadequately defined pharmacokinetic interaction. However, a direct antimigraine effect of caffeine may contribute to the claimed increased efficacy of ergotamine-caffeine combinations in relieving migraine attacks. Serotonin syndromes have been reported as probable pharmacodynamic consequences of the use of ergots or triptans in persons taking serotonin reuptake inhibitors. There have been two reports of involuntary movement disorders when sumatriptan has been used by patients already taking loxapine. Nearly all the clinically important interactions between the ergopeptide antimigraine agents and currently marketed drugs are likely to have already come to notice. In contrast, new interactions involving the triptans are likely to be recognised as additional members of this family of drugs, with their different patterns of metabolism and pharmacokinetics, are marketed.