Shortcut formulae for pharmacokinetic dosage adjustments.

Dosage adjustments can be difficult and time-consuming, especially for the non-specialist. The objective of this investigation was to obtain shortcut formulae to calculate dosage adjustments for (i) a drug obeying linear pharmacokinetics (i.e. first order) and given orally, by a continuous infusion or by an intermittent intravenous infusion; and (ii) a drug obeying Michaelis-Menten kinetics and given orally or by an intermittent intravenous infusion. Shortcut formulae are derived by assuming a steady-state model (e.g. one-compartment intermittent intravenous infusion) for a patient and drug and then dividing by the same equation, assuming a different dose and interval. The assumption underlying the division is that the patient's pharmacokinetic parameters do not change. The results obtained show that for drugs following linear pharmacokinetics and having the same dosage interval, the ratio of new dose : given dose is of course proportional to the ratio of desired steady-state concentration : measured steady-state concentration. If the interval is changed, then there are three variables: the dose, the steady-state concentration and the accumulation factor. The ratio of the doses is still proportional to the ratio of the steady-state concentrations but is also inversely proportional to the accumulation factors for the different dosage intervals. Furthermore, for intermittent infusions, the dosages calculated are equivalent to those obtained using the Sawchuk and Zaske method. With the shortcut formulae, it is more easily seen that most common dosage adjustments readily reduce to simple proportions or joint variation. These calculations can be quickly carried out with only the patient's terminal rate constant for linear pharmacokinetics and their Michaelis-Menten constant (Km) value for Michaelis-Menten kinetics. The methods are illustrated with actual patient examples.

On statins, strokes, meta-analyses, competing risks, and the onward march of science.

A comment on the conduct of a meta-analysis analyzing the effects of statins on cardiovascular and cerebrovascular outcomes is presented in this editorial. Competing risk and risk-stratified analysis models that may be more appropriate for the analysis of clinical trials in general and statin trials in particular are introduced. The avoidance of these more complicated models seems to be paradoxical when other models that clinicians have used for some time and are using today are seen to contain more patient variables than the proposed models. Certainly, one way these competing risk and general mathematical models will be used is to have the data readily available for other researchers to duplicate the calculations or use in entirely new ways. This aids in the learning process and helps students, reviewers, editors, and others who wish to research and judge the clinical trials.

Effects of antioxidants coenzyme Q10 and lipoic acid on interleukin-1 beta-mediated inhibition of glucose-stimulated insulin release from cultured mouse pancreatic islets.

During the development of the autoimmune disease, insulin-dependent diabetes mellitus (IDDM) islet cell death is thought to be mediated in part by oxygen and nitrogen free radicals and interleukin 1beta (IL-1beta), secreted by activated macrophages. Free radicals disrupt the homeostasis of biological systems by damaging major constituent molecules such as lipids, proteins, and DNA. Islet cells are quite susceptible to oxidative damage due to low levels of antioxidant enzymes involved in free radical consumption. If IDDM is associated with an imbalance of oxidative stresses and antioxidant responses in islet cells, then it may be possible to ameliorate disease by supplementating antioxidant defenses. In this study, the antioxidants coenzyme Q10 and lipoic acid were able to block IL-1beta-mediated inhibition of glucose-stimulated insulin secretion from islet cells at 10(-12) M and 10(-9) M, respectively.

Provision of drug information to patients by pharmacists: the impact of the Omnibus Budget Reconciliation Act of 1990 a decade later.

Drug-related illness in the United States factors substantially in health care costs, although often these illnesses and their attendant costs are preventable. One strategy for minimizing adverse drug reactions is to provide drug information to consumers in the form of prescription counseling at pharmacies. The Omnibus Budget Reconciliation Act of 1990 (OBRA 1990) contained provisions for mandating such counseling to Medicaid patients. OBRA 1990 was implemented in 1993, but most states acted quickly to extend counseling services to all patients receiving prescription drugs. We looked at the extent and quality of prescription counseling available in community pharmacies 1 decade after OBRA 1990 was written. We evaluated the counseling services afforded at large chain pharmacies, independent community pharmacies, and on-line pharmacies for a hydrochlorothiazide prescription. We found that most (69%) pharmacies offered to provide prescription counseling service, and that average counseling index scores, a measure of the quality or extent of information provided as determined by a Rasch analysis, were generally satisfactory. Our observations based on a single prescription for hydrochlorothiazide, along with other studies, suggest that there is a positive upward trend in the number of pharmacies providing prescription drug information, and that the extent of information provided suggests that the objectives of OBRA 1990 and related legislation to reduce ADRs are being fundamentally satisfied.