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J Devane

Publications and source records attributed to J Devane.

29 records · Page 2Linked to original sources
PubMed1991

In-vivo pharmacokinetic characteristics of a transdermal phenylpropanolamine (PPA) preparation.

Phenylpropanolamine hydrochloride (PPA-HCL) is a synthetic phenylisopropanolamine sympathomimetic agent which is structurally related to ephedrine and amphetamine. Although its precise mechanism of action has not been conclusively determined, PPA is known to exert cardiovascular effects possibly related to indirect stimulation of beta-adrenergetic receptors in the heart. In addition, through CNS stimulation, PPA is known to act as an appetite suppressant, the anorexigenic effect being much weaker than that of amphetamine. In order to develop a convenient dosage of PPA, a transdermal preparation containing 250 mg PPA has been developed. Transdermal delivery is convenient both in terms of case of application and ready withdrawal of drug if desired. Oral PPA dosage forms are designed to have a fall off period of 6-8 hours to facilitate sleep. Such a drug free period is easily attained using a transdermal system either by removal of the transdermal device or incorporation of a lag period into the design of the system. The bioavailability and in vitro pharmacokinetic characteristics of this novel PPA preparation were compared with those of a reference sustained-release 75 mg Q16 PPA tablet (Acutrim), in a pilot, 3 subject, unblinded, cross-over, single dose study. Subjects fasted from the evening before dosing until 0.5 hours prior to dosing. Patches were removed 24 hours following application. Reportedly effective plasma PPA levels for appetite suppression were recorded after patch application and were comparable to those observed with the reference. Peak plasma PPA levels were slightly higher for the transdermal patch compared with the tablet formulation (93.6 ng/ml versus 80.10 ng/ml respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous↗
PubMed1991

Distal ileum and colon: targeted sites for 5-ASA release.

Sulphasalazine, used in the treatment of ulcerative colitis, is cleaved in the colon by the metabolic action of colonic bacteria on the diazo bond to release 5-Aminosalicylic acid (5-ASA) and sulpharidine. Whilst the former has been demonstrated to be active moiety, the latter is reputed to be responsible for toxicity associated with sulphasalazine therapy. A new multi-particulate formulation of 5-ASA has been designed (Asalan) to achieve targeted release of the drug in both the distal small intestine and colon and hence may be beneficial in the treatment of not only Ulcerative Colitis but also Crohn's disease. An imaging study was performed with beads formulated with barium sulphate using the same procedure employed to prepare 5-ASA beads. This study suggested 5-ASA capsule disintegration and bead dispersal in both the distal ileum and colon. This targetting was confirmed in two further in vivo studies using the 5-ASA formulation itself. In the first study comparison of plasma ASA levels following treatment with sulphasalazine treatment confirmed that 5-ASA release was occurring proximal to the colon. Despite this earlier release, the percentage of administered dose that was unabsorbed (dose-urinary recovery) was approximately 90%. In a second study a comparison was made with a single unit tablet of 5-ASA. A greater consistency and accuracy of targetting, as revealed by the appearance of plasma ASA levels, was confirmed for the capsule formulation. These separate studies were undertaken to evaluate the in vivo intestinal release characteristics of this new 5-ASA formulation in healthy volunteers.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminosalicylic Acids↗
PubMed1991

Dose proportionality of pharmacokinetics with a cr-verapamil formulation.

The relatively short half life of verapamil necessitates divided daily dosing in the treatment of angina, hypertension and arrhythmia. To reduce dosing frequency and increase patient compliance and therapeutic efficacy, a controlled-release once-daily verapamil formulation (Verelan) has been developed in three dosage strengths, 120 mg, 240 mg and 360 mg. In order to investigate the dose linearity of this formulation in the 120 mg and 360 mg dose range, un unblinded, crossover, comparative evaluation of the three dosage strengths was performed in a population of 27 male volunteers. Each treatment period lasted nine days with a minimum of 7 days between periods. On Days 1 and 2 of each treatment period, the single dose phase was evaluated following administration of medication on Day 1 only with regular blood sampling over the 48 hour period. On Days 3 and 7 inclusive, the five-day steady phase was evaluated. Mean plasma profiles following administration of each dose demonstrated extended verapamil absorption up to 24 hours after dosing. In both the single dose and steady state phases a linear relationship was observed between increasing dose and pharmacokinetic response over the dose range of 120 mg and 360 mg. This linearity in response with increasing dose is in contrast to the non-linearity of verapamil's pharmacokinetics with conventional verapamil formulations previously described by an number of workers and may be due to a saturation of verapamil's hepatic first pass metabolic pathway.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Pharmacokinetic characteristics of a novel controlled-release sprinkle formulation of salbutamol.

Childhood asthma, which commonly effects between 5 and 12% of children, is often treated with the beta agonist salbutamol which relaxes bronchial smooth muscle, resulting in bronchodilation. Although a popular mode of administration, delivery of salbutamol by aerosol is not often practical, particularly in younger children. A need therefore exists for a pediatric salbutamol dosage form, which not only controls asthma but is also convenient and acceptable to use. Enhanced control of asthma may be achieved using a controlled-release formulation of salbutamol. This also serves to increase patient compliance which may be further improved, in the case of children, by presenting the formulation in a more acceptable paediatric dosage form. In this study, a novel controlled-release sprinkle formulation of salbutamol was compared with a reference salbutamol tablet (Proventil Repetabs). This was conducted as a six subject unblinded, single-dose, cross-over study comparing a single dose (8 mg) of salbutamol sprinkle with a single dose (2 x 4 mg) of the reference tablet. The salbutamol sprinkle was formulated using the controlled-release polymeric micromatrix pharmaZome technology and was administered as a single dose dispersed in a spoonful of jam. The time to peak concentration, half-life and peak-to-trough ratio were similar for both formulations. Mean plasma salbutamol levels and mean peak salbutamol levels were slightly lower for the sprinkle formulation when compared with the reference. This novel sprinkle formulation has potential as an effective controlled-release bronchodilator which also offers distinct advantages for paediatric dosing, in terms of ease and acceptability of administration.

Albuterol↗
PubMed1984

Effects of diuretics on the renal handling of magnesium.

Diuretic-induced magnesium losses may contribute significantly to magnesium deficiency. Loop diuretics especially cause major losses of urinary magnesium. Our initial experiments in saline-loaded rats indicated that frusemide greatly increased magnesium excretion, while bendrofluazide caused no significant change and triamterene actually decreased magnesium excretion. Therefore, not all diuretics are magnesium-wasting. There is evidence that the potassium-sparing diuretic amiloride may also exert magnesium-sparing properties. In saline-loaded rats, the magnesium-sparing effect of amiloride was demonstrated when the drug was administered either alone or in combination with frusemide. Renal clearance studies in rats indicated that the magnesium-sparing effect of amiloride was a direct renal action and not secondary to possible extrarenal actions. A dose-response relationship has been established for the effect of amiloride in reducing fractional excretion of magnesium and potassium during frusemide diuresis in rats. Congestive heart failure patients being treated with frusemide were found to be both potassium- and magnesium-deficient, as indicated by reduced lymphocyte concentrations of potassium and magnesium. In these patients, amiloride reduced urinary magnesium and potassium, increased plasma magnesium and potassium, and also increased lymphocyte magnesium and potassium. The effects of amiloride most likely involve enhanced reabsorption of magnesium, but further studies are required to establish the precise mechanism(s) involved in the drug's magnesium-sparing properties.

Amiloride↗
PubMed1983

Evidence for a magnesium-sparing action by amiloride during renal clearance studies in rats.

The potassium-sparing diuretic, amiloride, reduced the fractional excretion of magnesium in anaesthetized rats. Alterations in glomerular filtration rate (GFR), the filtered load of magnesium, arterial blood pressure, the status of the extracellular fluid volume, plasma aldosterone concentration and acid-base balance were not involved. It was concluded that amiloride exerted a magnesium-sparing effect by a direct renal action.

Aldosterone↗
PubMed1983

Dose-dependent reduction in renal magnesium clearance by amiloride during frusemide-induced diuresis in rats.

The effects of the potassium-sparing diuretic, amiloride, on fractional magnesium excretion were investigated at four doses (0.02, 0.08, 0.20 and 2.00 mg kg-1 h-1) during frusemide-induced diuresis. Amiloride caused a dose-dependent reduction in the fractional excretion of both magnesium and potassium, whereas the effects of amiloride, over the same dose range, on fractional sodium and calcium excretion were not dose-dependent. The results indicate that amiloride exerted a specific renal action to alter magnesium and potassium transport dissociated from effects on sodium excretion.

Amiloride↗
PubMedDate not supplied

Assessment of risk reduction strategies for the management of agricultural nonpoint source pesticide runoff in estuarine ecosystems.

Agricultural nonpoint source (NPS) runoff may result in significant discharges of pesticides, suspended sediments, and fertilizers into estuarine habitats adjacent to agricultural areas or downstream from agricultural watersheds. Exposure of estuarine fin fish and shellfish to toxic levels of pesticides may occur, resulting in significant declines in field populations. Integrated pest management (IPM), best management practices (BMP), and retention ponds (RP) are risk management tools that have been proposed to reduce the contaminant risk from agricultural NPS runoff into estuarine ecosystems. Field studies were conducted at three sites within coastal estuarine ecosystems of South Carolina (SC) from 1985 to 1990 that varied in terms of the amount and degree of risk reduction strategies employed. An intensively managed (IPM, BMP, and RP) agricultural treatment site (TRT) was studied for pesticide runoff impacts. From 1985 to 1987, there were minimal (some IPM and BMP) management activities at TRT, but from 1988 to 1990, TRT was managed using an intensive risk reduction strategy. A second unmanaged agricultural growing area, Kiawah (KWA), was also studied and compared with TRT in terms of pesticide runoff and the resulting impacts on grass shrimp (Palaemonetes pugio) and mummichogs (Fundulus heteroclitus). A third, non-agricultural, reference site (CTL) was used for comparing results from the managed and unmanaged agricultural sites. In situ toxicity tests and field samples of the grass shrimp populations were conducted at each site and compared in terms of survival and the effectiveness of current risk reduction strategies. Significant runoff of insecticides (azinphosmethyl, endosulfan, and fenvalerate) along with several fish kills were observed at TRT prior to the implementation of rigorous risk reduction methods. A significant reduction of in stream pesticide concentrations (up to 90%) was observed at TRT following the implementation of strict NPS runoff controls, which greatly reduced impacts on estuarine fish and shellfish. At the unmanaged KWA, continued impacts due to the runoff of these insecticides were observed, along with several fish kills. Additional monitoring indicated that gravid female grass shrimp populations from KWA had elevated levels of P-glycoprotein (P-gp), a multidrug resistance protein, which may transport various pesticides across cellular membranes. Comparison of field results with laboratory toxicity tests established that pesticide exposure was the primary cause of observed field impacts at each site. These findings clearly indicate the value of an integrated risk reduction strategy (BMP, IPM, and RP) for minimizing impacts from NPS agricultural pesticide runoff.

ATP Binding Cassette Transporter, Subfamily B, Mem↗