Differences In Drug Distribution Research Articles

Gender differences in drug therapy.

Patient response to drug therapy is affected by multiple factors, including age, renal function, diet, smoking, congestive heart failure and gender. However, the data on gender differences in pharmacotherapy are limited, predominantly because women are excluded from clinical research due to the potential risks involved during pregnancy and co-existing illnesses in elderly women. Currently some information is available on gender differences in drug therapy. Differences in drug distribution and response due to different body composition as well as the effects of hormonal differences are the few that have been documented. Differences in drug metabolism due to differences in blood concentration of enzymes such as alcohol dehydrogenase has been recently described. Pharmacotherapy may also have to be altered due to differences in disease expression, like increased vasomotor tone in women. Drug efficacy has been found to be affected by gender---an example is antiplatelet therapy for stroke prevention. Finally, the side effects of drugs may differ depending on gender. Those involved in pharmacotherapy should be aware of these differences when prescribing drugs to female patients, since the majority of clinical data regarding pharmaceuticals has been derived primarily from a population of young males.

The Pharmacokinetics of Avian Therapeutics

The knowledge of drug disposition and metabolism in various avian species is rapidly expanding. Allometric scaling, as a new method for extrapolating a dose from one species to the other, is a mathematical characterization of the functional consequences of change in mass. Special attention, in addition, has been paid to interspecies differences in relation to metabolic elimination, anatomy, and physiology of the digestive and respiratory systems and differences in drug distribution. Intraspecies differences attributable to physiochemical aspects of the drug preparation and physiologic conditions of the avian patient can also influence drug efficacy. The consequences of the choice of a particular method of drug administration in relation to avian therapy are also considered.

Chemical analysis of bis(5‐amidino‐2‐benzimidazolyl) methane in the arthritic rat knee using microdialysis and microcolumn liquid chromatography

AbstractMicrocolumn liquid chromatography and microdialysis were coupled together to study the distribution of an IV administered drug into the knee joint of a rat with acute arthritis. Dialysate from microdialysis probes located directly within the intraarticular region and in the surrounding muscle was delivered at a flow rate of 0.25 μL min−1 directly into a microcolumn LC system. A 0.5‐mm i.d. microcolumn and fluorescence detector were utilized. An in vitro model was developed to estimate the drug concentration in the dialysate. Differences in drug distribution between the intra and extraarticular knee regions were detected, and the potential utility of this technique in the pharmacokinetic evaluation of site‐specific drugs was demonstrated.

Pharmacotherapeutic aspects of medication of birds.

This review covers current knowledge of the pharmacodynamics and pharmacokinetics of drugs in avian species. Special attention has been paid to inter-species differences in relation to metabolic elimination, anatomy and physiology of the digestive and respiratory system, and differences in drug distribution. Intra-species differences attributable to physicochemical aspects of the drug preparation and physiological conditions of the avian patient can also influence drug efficacy. The consequences of the choice of a particular method of drug administration on pharmacokinetics are also considered.

Structure-activity relationships of phencyclidine derivatives in rat cerebellum

The depressant effects of phencyclidine [1-(1-phenylcyclohexyl) piperidine, PCP] and three of its analogs (m-amino-PCP, m-nitro-PCP, and PCP-methyliodide) on the spontaneous action potential discharge of cerebellar Purkinje neurons in urethane-anesthetized rats were examined in this study. Both intraperitoneal injection and micro-pressure ejection were employed as routes of drug administration. The relative potency after parenteral administration corresponded closely with previous findings in behavioral test paradigms. PCP and m-amino-PCP were equipotent, m-nitro PCP was less potent than either PCP or m-amino-PCP, and PCP-methyliodide showed almost no activity. After local administration onto neurons, m-amino-PCP was significantly more potent than PCP, while PCP, m-nitro-PCP, and PCP-methyliodide were equipotent. Tritiated PCP, m-nitro PCP, and m-amino PCP have similar distribution and metabolism in cerebellum. PCP-methyliodide, a quaternary ion, does not cross the blood brain barrier. M-nitro PCP is appreciably less ionized at pH 7.4 than PCP or m-amino-PCP and, therefore, may be more easily sequestered into lipids. Differences between PCP and its analogs found in experiments which employ parenteral administration may reflect differences in drug distribution. These differences are minimized when these drugs are administered directly onto neurons via pressure microejection.

Drug distribution and renal excretion in the elderly

Drug responsiveness in the elderly often differs from that in younger individuals. A causative factor is often thought to be age-related changes in the quantitative fashion in which the body handles the drug. It is speculated that changes in body size, composition, and tissue perfusion lead to differences in drug distribution . The limited supportive evidence for this is reviewed, along with the practical consequences in drug therapy. More definitive data is presented on the age-related impairment of renal function and its effects on the urinary elimination of drugs and metabolites. Methods are presented to permit rationale dosage regimen modifications for elderly patients with reduced renal function.

New approach to the hepatic first-pass effect by whole-body autoradiography.

Whole-body autoradiography was used to investigate the influence of the route of administration and dose on the distribution of drugs in the rat. Propranolol and imipramine were used as model drugs with a relatively high hepatic extraction ratio, and salicylic acid and antipyrine were used as model drugs with a relatively low hepatic extraction ratio. Each drug was administered at the same radioactivity level to rats by intravenous infusion or portal venous infusion over 30 s, regardless of the total dose and route of administration. An autoradiogram obtained 3 min after portal venous infusion was compared with that obtained 3 min after intravenous infusion. The radioactivity of propranolol that reached the systemic circulation was highly dependent on both the route of administration and dose, while that of imipramine was dependent only on the route in the dose range studied. The radioactivity of salicylic acid and antipyrine was distributed in the whole body independently of the route of administration and dose. The two drugs having a higher hepatic extraction ratio showed an uneven distribution in the liver after portal venous administration, but the two drugs having a lower hepatic extraction ratio did not. It was shown that the technique of portal venous administration for whole-body autoradiography is useful to visualize differences in drug distribution depending on the route of administration and dose and to study hepatic tissue binding in the first-pass extraction of drugs.

Kinetics of intravenous chlordiazepoxide: Sex differences in drug distribution

Fourteen healthy subjects (7 male and 7 female) received 50 mg of chlordiazepoxide (CDX) hydrochloride by I‐hr intravenous infusion. Multiple venous blood samples drawn during the 72 hr after the infusion were assayed for whole blood concentrations of CDX and of its major metabolite, desmethylchlordiazepoxide (DMCDX). Mean (±SE) pharmacokinetic parameters, determined by weighted nonlinear least‐squares regression analysis, were: distribution half‐life, 1.3 (±0.3) hr; elimination half‐life, 17.8 (±2 .2) hr; volume of central compartment (VI), 0.27 (±0.02) Llkg; total distribution space (V.J, 0.52 (±0.03) Llkg; total clearance, 26.4 (±3.2) mllmin. Viand Vd were significantly larger among females (0.30 and 0.58 Llkg) than among males (0.22 and 0.45 Llkg), suggesting more extensive drug distribution in females. Values of half‐life and of clearance did not, however, differ significantly between sexes. A second study in three subjects compared simultaneous whole blood and plasma CDX concentrations after intravenous bolus injection and showed them to be highly correlated. Red cell :plasma partition ratios were 0, O.OJ, and 0.24, indicating limited uptake of CD X by red cells. Volumes of distribution and clearances calculated from CDX concentrations in whole blood are larger than those based on plasma concentrations.

Nonlinear Pharmacokinetic Model of Intravenous Anesthesia

A nonlinear pharmacokinetic model was constructed to describe the body distribution of intravenous anesthetics, using the physiological modeling approach for drug distribution kinetics. The model considers the physiological parameters of tissue volumes and blood flow rates for the standard four phases of blood, viscera, lean tissue, and adipose tissue and also the associated drug parameters known to influence drug distribution. A simple ramp function having a characteristic time (volume per flow rate) is used to describe the rate of approach to equilibrium conditions for each tissue phase. The model was evaluated for the distribution of methohexital and thiopental by comparing calculated values to experimental drug concentrations taken from the literature. The physiological alteration of obesity also was programmed into the model to evaluate its capability for predicting the influence of body alterations on drug distribution. The results indicated that a preliminary mathematical model of relatively simple design is capable of at least a semiquantitative prediction of intravenous anesthetic drug concentrations in body tissues and has the potential of accounting for differences in drug distribution in the presence of selected physiological alterations.