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R L Parsons

Publications and source records attributed to R L Parsons.

140 records · Page 8Linked to original sources
PubMed1970

Factors in the inactivation of postjunctional membrane receptors of frog skeletal muscle.

Several factors which influence the rate of inactivation of muscle postjunctional membrane (PJM) receptors during the sustained application of carbamylcholine (CARB) have been studied by two methods. The rate of inactivation was increased by elevating the tonicity of the bathing medium, by increasing the CARB concentration, by raising the calcium ion concentration, and by substituting SO(4) (=) for Cl(-) ions in the extracellular fluid. The relative effectiveness of calcium and other divalent cations in receptor inactivation was compared. In the absence of calcium, other divalent cations such as magnesium, strontium, or manganese were not efficient substitutes for calcium. In the presence of calcium, the addition of strontium or manganese ions accelerated the rate of receptor inactivation, but the addition of magnesium (up to 12 mM) inhibited this process. The inactivation of the membrane receptors in denervated muscle fibers was found to be similar to that in innervated muscle fibers. Various factors in PJM receptor inactivation are discussed. It is suggested that PJM receptor inactivation is influenced by the binding of calcium ions to sites on the internal surface of the PJM.

Acetylcholine↗
PubMed1970

Influence of polyvalent cations on the activation of muscle end plate receptors.

The influence of polyvalent cations on the activation of end plate receptors has been studied in vitro on the sartorius muscle of the frog. In the absence of extracellular calcium, the sensitivity of the receptors to depolarizing quaternary ammonium salts was markedly reduced. Maximum receptor activation occurred in those fibers equilibrated in 1.8 mM calcium Ringer solution, with the response being reduced as the calcium concentration was raised or lowered. Magnesium was less efficient than calcium in regulating the sensitivity of the end plate receptors, the maximum receptor response occurring in those fibers equilibrated in 8 mM magnesium Ringer solution. In the presence of lanthanum the end plate response to carbamylcholine or acetylcholine was enhanced. Lanthanum increased the conductance change produced by carbamylcholine both in polarized and in potassium-depolarized fibers. The application of 10(-2) mM lanthanum to the end plate increased MEPP's amplitude, rise time, and half-fall time by 19, 54, and 45%, respectively. The results suggest that polyvalent cations influence postjunctional membrane receptor processes in addition to their well-documented prejunctional action.

Acetylcholine↗
PubMedDate not supplied

Comparative pharmacokinetics of ketoprofen derived from single oral doses of ketoprofen capsules or a novel sustained-release pellet formulation.

Nine healthy male volunteers took part in a crossover study to compare the pharmacokinetics of ketoprofen after administration of a single oral dose (200 mg) of ketoprofen as 'Orudis' capsules or encapsulated sustained-release pellets, 'Oruvail'. The mean +/- standard deviation values for highest observed plasma ketoprofen concentrations were determined by high performance liquid chromatography to be 23 +/- 11 micrograms ml-1 at 0.82 +/- 0.18 h after dosing with ketoprofen capsules and 3.5 +/- 1.0 micrograms ml-1 at 4.9 +/- 1.0 h after dosing with sustained-release pellets. The apparent ketoprofen elimination half-lives after these treatments were 3.3 +/- 1.2 h and 8.4 +/- 3.4 h, respectively. The systemic availability of ketoprofen was essentially the same after each treatment. Administration of sustained-release pellets (containing 200 mg ketoprofen) once every 24 h is predicted to produce similar average and markedly higher minimum plasma ketoprofen concentrations than are produced by ketoprofen capsules (100 mg) every 12 h, and similar minimum plasma ketoprofen concentrations to those achieved by dosing ketoprofen capsules (50 mg) every 6 h. Once-daily administration of a non-steroidal anti-inflammatory agent has an obvious therapeutic advantage over more frequent dosing. This study suggests that the sustained-release pellet formulation described herein is a suitable formulation for once-daily administration of ketoprofen.

Administration, Oral↗
PubMedDate not supplied

Urinary pharmacokinetics of orally administered ketoprofen in man.

The urinary pharmacokinetics of ketoprofen were compared after administration of single doses of standard ketoprofen capsules or two sustained-release pellet formulations of ketoprofen to nine healthy volunteers, using a specific and sensitive high-performance liquid chromatographic assay procedure. The sustained-release pellet formulation with the faster in vitro release characteristics was shown to be bioequivalent to ketoprofen capsules ('Orudis'). The mean (+/- standard deviation) apparent elimination half-life of ketoprofen after this sustained-release formulation was 7.4 +/- 3.1 h, compared with 4.1 +/- 0.85 h after ketoprofen capsules. The sustained-release formulation with the slower in vitro dissolution characteristics also exhibited slower in vivo dissolution, but was only 65% bioavailable, compared to ketoprofen capsules. A disproportionately large degree of elimination of free ketoprofen was observed between 0-6 h after dosing with ketoprofen capsules. This result could be explained by a saturable mechanism in the metabolism of ketoprofen to its glucuronide. however, since the renal excretion of free ketoprofen is not a major route of ketoprofen elimination, relatively large alterations in this parameter will not markedly alter elimination half-life or area under the plasma ketoprofen concentration against time curve. Thus, the clinical significance of such a mechanism is probably negligable.

Administration, Oral↗
PubMedDate not supplied

Drug absorption in gastrointestinal disease with particular reference to malabsorption syndromes.

There is a considerable range in the dose of many drugs that is required to produce a given pharmacological effect in an individual patient. This individual variation in dose requirement is sometimes reflected in the wide scatter in the steady state plasma concentration that follows the same oral dose of a drug given to any group of subjects. Such individual differences are largely due to variation in the rate of elimination of drugs. Gastrointestinal disease may also alter oral dose requirements by producing variation in both the amount and rate of drug absorption. These changes may be reflected in the plasma concentration/time curve that follows an oral dose. The amount of drug abosorbed is simultaneously affected by many factors. These include the physicochemical properties of the drug and the physiological factors that operate within the gut, as well as the presence of other substances such as food, or interaction with other drugs in the gut. The availability of the drug within the intestinal lumen is largely governed by its dissolution characteristics, particularly factors which can interfere with dissolution of the drug product in the gut. Physiological factors within the gut that affect oral drug absorption include gastric emptying rate and intestinal motility, the pH of the gastrointestinal fluids, the activity of gastrointestinal drug metabolising enzymes (e.g. monoamine oxidase and dopa decarboxylase) or drug metabolising bacteria and the surface area of the gut. Many factors affect gastric emptying. These include disease, surgery and other drugs. A change in the rate of gastric emptying alters the rate of drug delivery from the stomach to the duodenum and upper small intestine. This may profoundly alter the plasma concentration/time curve that follows oral administration of many drugs. For some drugs, proximal jejunal disease may reduce, delay or increase the apparent amount of drug absorbed. Reduced absorption of an antibiotic leads to a fall in the peak plasma concentration. If the peak falls below the minimum inhibitory concentration for a particular organism then therapeutic failure may occur, if it is assumed that the peak plasma concentration is all important for antimicrobial activity. Excessive drug absorption may lead to drug toxicity. Abnormal drug absorption is a feature of lower small intestinal conditions such as Crohn's disease. This suggests that drug absorption is not confined to the jejunum but continues throughout the small intestine. It is not always possible to predict the pattern of drug malabsorption from a knowledge of the physicochemical and pharmacokinetic properties of the drug and the pathophysiology of the disease. The rate and amount of drug absorbed be one patient may differ from that in another patient with the same condtion. Although these differences reflect normal individual variation, they are also related to the extent and activity of disease at the time of study...

Absorption↗