Stability of the nitrogen mustard mechlorethamine in novel formulations for dermatological use.

Long term stability measurements were made for the nitrogen mustard mechlorethamine HCl at a concentration of 0.02% in six topical formulations: Aquaphor ointment, Transcutol, Labrasol, 10% Transcutol in Aquaphor, 10% Transcutol in Labrasol, and Aquaphilic ointment. The drug decomposed gradually in Aquaphor ointment at room temperature, dropping to 95% in 4 weeks, 85% in 12 weeks, and 78% in 39 weeks.

Modifications and insights into a method for the analysis of the nitrogen mustard mechlorethamine by high-performance liquid chromatography.

Previously, a method was presented for the analysis of mechlorethamine by derivatization of this unstable nitrogen mustard to bis(2-phenylthioethyl)methylamine (PTEMA), a stable compound suitable for analysis by HPLC with UV detection [J.C. Reepmeyer, J.

Pharmacokinetics of prednisolone in man during acute and chronic exposure to high altitude.

Introduction: The exposure to high altitude (H) produces several physiologic alterations which may induce changes in the pharmacokinetics of drugs. This hypothesis has been confirmed in previous studies which suggest that drugs which are highly bound to plasma proteins are most likely to exhibit altered pharmacokinetics.

Objectives: To further elucidate the influence of H on pharmacokinetics, prednisolone was selected, since it is highly bound to plasma proteins, renally excreted and poorly bound to red blood cells.

Effects of high altitude exposure on the pharmacokinetics of furosemide in healthy volunteers.

Introduction: A cascade of pathophysiological events occurs with the ascension to high altitude (H). We have performed studies on the effects of exposure to H on the pharmacokinetics of drugs. The hypothesis behind these studies has been that the exposure to H, which produces marked physiological changes in the body, may alter pharmacokinetics, and consequently, pharmacodynamics.

Pharmacokinetics of lithium in healthy volunteers after exposure to high altitude.

Introduction: Exposure of the human body to high altitude causes a number of physiological changes. In previous studies, we observed that these changes may alter the pharmacokinetics of drugs. The number of erythrocytes/mm3 increases both, after acute exposure to high altitude (HA), i.

Effect of insulinlike growth factor-1 treatment in children with cystic fibrosis.

Objectives: Malnutrition is common in cystic fibrosis (CF) and adversely affects survival. Because insulinlike growth factor-1 (IGF-1) has insulinlike effects in terms of carbohydrate metabolism and is growth promoting, the authors hypothesized that its use would increase linear growth rate and decrease insulin requirements in children with CF.

Methods: The authors used a double-blind placebo-controlled crossover design.

Pharmacokinetics of acetazolamide in healthy volunteers after short- and long-term exposure to high altitude.

Exposure to high altitude results in significant physiologic changes and may precipitate mountain sickness, ranging from mild symptoms above 2,500 m to severe symptoms above 4,000 m. In a previous study, changes in the pharmacokinetics of meperidine were observed after exposure to high altitude. This study was conducted to investigate whether similar changes occur for acetazolamide, which is prescribed for prophylaxis of acute mountain sickness.

Urinary excretion of acetazolamide in healthy volunteers after short- and long-term exposure to high altitude.

Acetazolamide is recommended for the prophylaxis of acute mountain sickness symptoms which sets in on climbing to high altitudes (H) above 2,500 m. It is primarily excreted unchanged in urine. In a previous study, we reported on the changes in urinary excretion of meperidine and its metabolite normeperidine on exposure to high altitude.

Animal models for transdermal drug delivery.

The purpose of this investigation was to compare the permeation characteristics of two different compounds (extremely polar and nonpolar), i.e., tritium-labeled water (W) and 14C-labeled 7-hydroxycoumarin (7-OHC), among 16 different species, including human skin.

The effects of triethanolamine myristate, a fatty acid salt, on the availability of riboflavin in humans.

A human study examined the effect of administering a triethanolamine myristate tablet 30 min prior to or concomitantly with a fast release riboflavin tablet and a slow release riboflavin tablet. There was no significant difference between any of the treatments although treatments with the slow release riboflavin resulted in greater urinary excretion of riboflavin. It is possible that a difference may only be seen within subjects because gastric emptying has a large intraindividual variation.

The effects of triethanolamine myristate, a fatty acid salt, on the bioavailability of riboflavin in dogs.

A study in dogs was performed in which a physiologic approach to delaying gastric emptying was examined. Triethanolamine myristate (a fatty acid salt) was used to delay gastric emptying in hopes of increasing the bioavailability of riboflavin. A bilayer tablet consisting of triethanolamine myristate and riboflavin resulted in an absolute bioavailability of 2-3 times greater than the bioavailability of riboflavin alone.

Microemulsion technology in the reformulation of cyclosporine: the reason behind the pharmacokinetic properties of Neoral.

Management of transplant patients receiving cyclosporine therapy is complicated by interpatient and intrapatient variability in pharmacokinetic parameters caused by the drug's unpredictable bioavailability. Cyclosporine, a highly lipophilic cyclic polypeptide, has recently been reformulated using a microemulsion delivery system to improve its bioavailability. This new orally administered formulation, Neoral (cyclosporine capsules and oral solution for microemulsion), has self-emulsifying properties and spontaneously forms a microemulsion (particle size < 0.

Pharmacokinetics of meperidine in healthy volunteers after short- and long-term exposure to high altitude.

Increased numbers of erythrocytes have been shown ex vivo to increase meperidine uptake, and one of the major physiologic changes that occurs at high altitude is an increase in hematocrit and erythrocytes. A study was therefore conducted to evaluate the effects of high altitude on the pharmacokinetics of meperidine. Intramuscular doses (0.

Pharmacokinetics of melatonin in human sexual maturation.

To determine whether melatonin pharmacokinetics change during puberty, we infused melatonin iv in 9 prepubertal, 8 pubertal, and 16 adult subjects and measured melatonin in serum and saliva, and 6-hydroxymelatonin sulfate in urine. A pilot study of 3 adult males showed dose linearity, absence of saturation kinetics, and unaltered metabolism and urinary excretion for doses of 0.1, 0.

Urinary excretion of meperidine and normeperidine in man upon acute and chronic exposure to high altitude.

The urinary excretion of unchanged meperidine (M) varies with change of pH and metabolism. Since exposure of man to high altitude (H) may cause significant physiologic changes, we investigated its effects on the urinary excretion of M. The study was carried out in 3 groups of healthy, male volunteers (ages 18-20 years): at sea level (L), at 4360 m the day after arrival at H (HA), and at 4360 m in subjects residing for > 10 months at H (HC).

Application of neural networks for the prediction of human pharmacokinetic parameters.

Artificial neural network (ANN) is a method used in the prediction of response variables from a set of input and target parameters. The most commonly used network in the area of pattern recognition is the feed forward/back propagation (BPN) network. A method to predict human pharmacokinetic parameters has been proposed using BPN with a combination of physicochemical properties and animal pharmacokinetic parameters.

Meperidine uptake and binding to human blood ex vivo.

Many drugs are bound to plasma proteins (PR) and/or to erythrocytes (RBC). The RBC count may change due to physiologic factors such as exposure to high altitude, or pathologic conditions such as anemia or as consequence of cancer treatment. The purpose of the investigation was to study the influence of 1) drug concentration, and 2) number of RBC on erythrocyte uptake or binding using meperidine as a model drug (M).

A biopharmaceutic approach in designing a controlled release tablet of sodium monofluorophosphate: 1. In vitro and in vivo studies in beagle dogs.

The purpose of this study was to develop a controlled release tablet (CRT) of sodium monofluorophosphate (NaMFP) based on biopharmaceutic and pharmacokinetic principles. NaMFP was introduced in the early eighties to treat osteoporosis. The required dose size (200 mg of NaMFP) and time of drug delivery (8.

Biopharmaceutic approach in designing a controlled release tablet of sodium monofluoro phosphate. Characterization of absorption sites and evaluation of modified dosage form.

Based on the results from in vivo study in dogs, it was decided to characterize the absorption sites of sodium monofluoro phosphate (NaMFP). It was hypothesized that bioavailability upon p.o.

Introduction to gene technology.

The increased use of biotechnology for numerous categories of common products (pharmaceuticals, foods, agricultural chemicals, etc.) has an ever increasing impact on our society. In the medical/pharmaceutical field, biotechnology signifies a drastic change in the approach to drug discovery, research and development, diagnosis, and disease management.

Development of an azopolymer based colonic release capsule for delivering proteins/macromolecules.

The colon, high in microbial contents with degradation ability of azo bonds, seems to be suitable for site-specific delivery of drugs. The degradation of azoaromatic hydrogel depends on the degree of swelling. However, the degree of swelling of azopolymers and the ability of the azoaromatic polymers to protect peptide drugs against the action of digestive enzymes still remains to be established.