Gender-related differences in xenobiotic metabolism.
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Animals↗
Biomedical subjects
P L Bonate
Publications and source records attributed to P L Bonate.
Serotonin receptor subtypes: functional, physiological, and clinical correlates.
The effects of 5-HT are varied and widely distributed throughout the human body. At this time, 5-HT research is a field ripe for "plucking." Not only is there a great demand for more selective agonists and antagonists, but there is more than enough work needed in receptor binding studies to keep pharmacologists employed for years to come. The clinical benefits of 5-HT receptor pharmacology are just starting to be developed and explored. Novel treatments for hypertension, migraine headaches, anxiety, and depression using 5-HT are just the beginning. It will be exciting to see what the future holds for 5-HT clinically.
Animals↗
Pathophysiology and pharmacokinetics following burn injury.
Therapy for inpatient burn victims is a clear challenge for the clinician, since directly following injury the pharmacokinetic parameters of many drugs will change drastically. Blood flow to the tissues is decreased; the rate of distribution and elimination of intravenous drugs administered during this time is reduced, and absorption of oral drugs may be slowed. Approximately 48 hours after injury, the blood flow increases, as does internal core temperature; the rates may increase as a result. Immediately after injury, plasma albumin level rapidly decreases and remains significantly depressed even at 60 days post-burn. Thus, the protein binding of acidic and neutral drugs will decrease and higher amounts of free fraction will be available at the biophase. On the other hand, alpha 1-acid glycoprotein increases in concentration and remains elevated at least 20 days post-burn. Basic drugs exhibit increased protein binding and will most probably need an increased dosage to achieve the appropriate pharmacological effect. Hepatic metabolism is also affected: the rate of phase I metabolism will decrease while phase II metabolism is unimpaired and may possibly increase. Other liver functions, such as protein synthesis, are also impaired. The effect on phase I drug metabolism is believed to be due to oxygen-derived free radicals released during the course of injury. In those patients with full-thickness burns, the epidermal layer is destroyed. Topical drugs have less of a barrier to cross and, consequently, less drug is needed to achieve effectiveness. In addition, the stomach has been found to secrete excess protons which will eventually lead to ulcers in the majority of patients. Hyperchlorhydria may affect the dissolution and disintegration of orally administered drugs in tablet form, as well as the partitioning of the neutral un-ionised species between the stomach and bloodstream. In the small intestine decreased nutrient absorption and DNA synthesis occurs, but the effect this may have on drug absorption is questionable. This paper focuses on the epidemiology of burn injuries and the way in which the pathophysiology following such injury alters the pharmacokinetics of a drug. Specific examples are provided. Some mention is made of burn management, therapeutic drug monitoring in burn patients, experimental design considerations, and future research topics.
Animals↗
Quantification of albumin in cerebrospinal fluid.
A standard spectrophotometric method for the quantitation of urinary albumin using bromphenol blue is evaluated to determine whether this method could be used to quantify cerebrospinal fluid albumin. In the modified procedure, 200 microliters of sample is added to 3 ml of bromphenol blue solution and the absorbance is read spectrophotometrically at 610 nm. Using standards and controls, the results were compared with known values and found to be both precise and accurate. The bromphenol blue method was compared with an immunoturbidometric method and found to be more precise and accurate, easier to perform, and cost effective. When compared to other dye-binding methods the bromphenol blue method is unique in its extremely low linear range and limit of detection. A minor disadvantage was the increased sample size necessary to obtain the increased precision.
Albumins↗