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Biomedical subjects

K P Flora

Publications and source records attributed to K P Flora.

At least 19 recordsLinked to original sources
PubMed1991

Pharmacokinetics of 2',3'-dideoxyinosine in patients with severe human immunodeficiency infection. II. The effects of different oral formulations and the presence of other medications.

2',3'-Dideoxyinosine (ddI) has shown activity against human immunodeficiency virus in phase I clinical trials. The drug is rapidly degraded by acid, however, thus raising questions as to the efficiency and reproducibility of its absorption after oral administration. This investigation studies the bioavailability of several oral dosage forms of ddI. When ddI was given to fasting patients as an oral solution with antacid, the bioavailability was 41% +/- 7% (mean +/- SEM). However, when given as buffered tablets, the bioavailability was considerably less (25% +/- 5%). The bioavailability increased slightly when the tablets were given with supplemental antacid (36% +/- 6%). Two enteric-coated preparations had reasonable bioavailability (36% +/- 5% and 26% +/- 5%), but the peak plasma level was much lower and occurred at a much later time than with the oral solution. When ddI was given as a premeasured powder containing sucrose and buffer to be reconstituted by the patient (the "sachet" preparation), the bioavailability was 29% +/- 6%. This was similar to that of the oral solution for this particular group of patients (30% +/- 7%). However, the bioavailability of the sachet was only 17% +/- 4% when administered with food. When the sachet was given to patients receiving ranitidine, no consistent change in bioavailability was noted. Also, no change in ddI pharmacokinetics was noted in patients receiving ganciclovir.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Stability of morphine sulfate in infusion devices and containers for intravenous administration.

The stability of morphine sulfate in one brand of polyvinyl chloride (PVC) container, one brand of glass syringe, and two brands of disposable infusion devices was determined. Solutions of morphine sulfate 2 and 15 mg/mL were used to fill the PVC containers and drug administration devices. Stability was determined for both concentrations of morphine sulfate at room temperature (23-25 degrees C) and 4 degrees C in the PVC containers, glass syringes, and disposable infusion devices; stability was also determined at 31 degrees C in the disposable infusion devices. At 0, 1, 2, 4, 7, 12, and 15 days, portions of the solutions were removed and assayed in triplicate by a stability-indicating high-performance liquid chromatographic method. At each time point the drug-infusion fluid combinations were inspected visually for color changes and the presence of particulate matter, and pH was measured. Morphine sulfate 2 and 15 mg/mL remained stable for at least 12 days in all the containers and devices at each temperature tested. No substantial changes in the pH or physical appearance of the solutions were observed. Morphine sulfate can be repackaged in the disposable glass syringe, PVC container, and both disposable infusion devices for routine clinical use.

Chromatography, High Pressure Liquid↗
PubMed1990

Stability of heroin hydrochloride in infusion devices and containers for intravenous administration.

The stability of heroin hydrochloride in various drug-administration devices was studied. Heroin hydrochloride was supplied as the bulk powder by the National Institute on Drug Abuse and in the formulated dosage form by Evans Medical, Ltd. Stability was determined at concentrations of 1 and 20 mg/mL at room temperature (23-25 degrees C) and at 4 degrees C in a polyvinyl chloride (PVC) bag, a disposable glass syringe, and two disposable infusion devices. Studies at both concentrations also were conducted at 31 degrees C in the disposable infusion devices. All experiments were conducted in triplicate. A validated, stability-indicating, high-performance liquid chromatography assay was used. Heroin hydrochloride remained stable for a minimum of 15 days in the PVC bag and the Infusor infusion device at the tested temperatures and concentrations. In the glass syringe, heroin hydrochloride was shown to be stable for a minimum of 15 days at both 1 mg/mL and 20 mg/mL if refrigerated at 4 degrees C, whereas at room temperature it was stable for a minimum of 7 days at 1 mg/mL and for 12 days at 20 mg/mL. In the Intermate 200 infusion device, heroin hydrochloride was stable for a minimum of 15 days at both concentrations and all temperatures except for the 1 mg/mL concentration at 31 degrees C. In the latter case, stability was for a minimum of two days. No substantial changes in physical appearance or pH were observed in any of the containers under the conditions studied. Heroin hydrochloride can be repackaged in the disposable glass syringe, PVC bag, and each of the disposable infusion devices for routine clinical use.

Chromatography, High Pressure Liquid↗
PubMed1989

Stability of pibenzimol hydrochloride in commonly used infusion solutions and after filtration.

The stability of pibenzimol hydrochloride was evaluated after reconstitution, after addition to several intravenous fluids, and after filtration. Vials containing pibenzimol hydrochloride 50 mg were reconstituted with 2.5 mL of 0.9% sodium chloride injection to 20 mg/mL. For determination of drug stability in intravenous fluids, vial contents were further diluted to 0.15 mg/mL by injection into glass containers and polyvinyl chloride (PVC) bags containing 250 mL of 5% dextrose injection, 0.9% sodium chloride injection, or lactated Ringer's injection. Pibenzimol concentrations were determined immediately after preparation and at various intervals after storage at 4-6 degrees C or 25 degrees C by means of a stability-indicating, high-performance liquid chromatographic technique. Vial contents were inspected visually for color changes, and pH was measured. Determinations were also made of the stability of pibenzimol 0.15 mg/mL in 0.9% sodium chloride injection after simulated infusions using a 0.22-micron filter set at 25 degrees C. All study solutions and admixtures retained more than 90% of the initial pibenzimol concentration. The greatest loss of drug (6-7%) occurred after 24 hours in lactated Ringer's injection in both glass and PVC containers and in 0.9% sodium chloride injection in PVC bags. No drug loss occurred as a result of filtration. Reconstituted pibenzimol hydrochloride and admixtures of pibenzimol in 5% dextrose injection, 0.9% sodium chloride injection, or lactated Ringer's injection in glass or PVC containers are stable for at least 24 hours at 25 degrees C. Filtration has no effect on stability.

Benzimidazoles↗
PubMed1987

Stability of cisplatin, iproplatin, carboplatin, and tetraplatin in commonly used intravenous solutions.

The stability of cisplatin, iproplatin, carboplatin, and tetraplatin in common intravenous solutions was studied. Admixtures of each drug in each of the following vehicles were prepared in glass containers: 0.9% sodium chloride injection, 5% dextrose injection, 5% dextrose and 0.9% sodium chloride injection, 5% dextrose and 0.45% sodium chloride injection (admixtures were prepared in plastic bags also), and 5% dextrose and 0.225% sodium chloride injection. Drug concentrations were monitored for 24 hours using stability-indicating high-performance liquid chromatographic methods. The stability of cisplatin and tetraplatin was related to the chloride ion content of the infusion fluid; when the infusion fluid contained 0.9% sodium chloride, each of these drugs was present at greater than 90% of the original concentration after six hours. The stability of iproplatin was not related to chloride concentration. A slight increase in the decomposition rate of carboplatin was observed in the presence of chloride ion. Carboplatin and iproplatin are stable for 24 hours in all the infusion fluids studied, but carboplatin should not be diluted with solutions containing chloride ions because of possible conversion to cisplatin. Cisplatin is stable for 24 hours in admixtures containing sodium chloride concentrations of 0.3% or greater. Tetraplatin is stable for six hours in admixtures containing sodium chloride concentrations of at least 0.018%.

Antineoplastic Agents↗
PubMed1985

Disposition and bioavailability of various formulations of tetrahydrocannabinol in the rhesus monkey.

Oral delta 9-tetrahydrocannabinol (THC) in gelatin capsules is under evaluation as an antiemetic agent in cancer patients, but knowledge concerning its bioavailability is incomplete and, furthermore, alternative routes of administration may be desirable. In this study, the disposition of THC was determined in four rhesus monkeys given 2.5-mg/kg doses using the following routes of administration and formulations: intravenous (iv); orally (po) on a cookie and in gelatin capsules; intramuscularly (im) in Tween-80 and in Emulphor-EL620; rectally in various suppository bases. Serum THC concentrations were measured by RIA and analyzed by weighted nonlinear regression. Serum concentrations were best described by a sum of two exponentials with alpha and beta half-lives (mean +/- SD) of 0.74 +/- 0.59 and 14.9 +/- 12.5 h. Apparent bioavailability (%F +/- SD) of various formulations of THC were: gelatin capsules, 26 +/- 14; cookie, 89 +/- 16; intramuscularly in Tween-80 and in Emulphor, 39 +/- 13 and 102 +/- 15, respectively. Using the method of statistical moments, mean residence times in the body (h +/- SD) were: intravenous, 6.08 +/- 1.60; cookie, 21.92 +/- 3.11; gelatin capsule, 26.80 +/- 23.61; intramuscularly in Emulphor, 10.92 +/- 3.46 (in Tween-80, not calculated). THC was not bioavailable by the rectal route. We conclude from this study that THC formulated as a gelatin capsule exhibits a low and variable extent of bioavailability and that intramuscular THC may be a useful alternative route of administration since it is more completely bioavailable.

Administration, Oral↗
PubMed1984

Stability of azacitidine in infusion fluids.

The stability of azacitidine in four infusion fluids was studied. Azacitidine was reconstituted and diluted to final concentrations of 0.2 mg/ml and 2.0 mg/ml in glass bottles and plastic i.v. bags containing 0.9% sodium chloride injection, 5% dextrose injection, lactated Ringer's injection, or Normosol -R. All admixtures containing azacitidine 2.0 mg/ml and both drug concentrations in Normosol -R were prepared in glass bottles only. The pH of each solution was measured before mixing, immediately after mixing, and after six hours. Duplicate samples of each solution were removed for assay by high-performance liquid chromatography at zero time, then at hourly intervals for six hours, and again at 25 hours. Three experimental runs were performed for each combination of drug concentration, infusion fluid, and type of container. The percentage of initial (zero time) concentration remaining was determined and plotted versus time. This plot was used to calculate the t90 (time at which 90% of the initial concentration remained) for each solution. The t90 values did not exceed three hours for any of the solutions studied. At the 0.2 mg/ml concentration, the t90 value in 5% dextrose injection (0.8 hours) was much smaller than that of the other solutions, which had t90 values of about two hours. In plastic bags, the percentage of initial azacitidine concentration remaining after six hours was less in 5% dextrose injection than in any other solution. The t90 values for all solutions containing azacitidine 2.0 mg/ml were similar, ranging from 2.4 to 3.0 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

Azacitidine↗
PubMed1984

Stability of cytarabine, methotrexate sodium, and hydrocortisone sodium succinate admixtures.

A high-performance liquid chromatographic (HPLC) method was developed for simultaneous determination of cytarabine, methotrexate sodium, and hydrocortisone sodium succinate, and the stability of the three drugs mixed together in four infusion fluids was assessed. Solutions were prepared with two concentrations of the three drugs similar to those administered intrathecally. Admixtures were prepared in Elliott's B solution, 0.9% sodium chloride injection, 5% dextrose injection, and lactated Ringer's injection. and lactated Ringer's injection. Solutions were filtered and kept in a disposable syringe in a 25 degrees C water bath for 24 hours. An HPLC assay capable of separating the three drugs and their degradation products was developed and validated. With one exception, all three drugs were stable in all four solutions for 24 hours. Hydrocortisone sodium succinate concentrations decreased to less than 90% of initial concentration in one of the admixtures with Elliott's B solution. No precipitation was noted in any admixture during the first eight hours of storage, but longer storage led to precipitation of unknown substances in some solutions. Admixtures of these three drugs in the four solutions tested are stable for at least 10 hours at 25 degrees C. However, intrathecal and administration of such admixtures within several hours of preparation is encouraged since none contains antibacterial preservatives.

Chemistry, Pharmaceutical↗
PubMed1982

Determination of ellipticine in biological samples by high-performance liquid chromatography.

Ellipticine, a plant alkaloid effective against murine leukemias and solid tumors, is presently undergoing toxicological assessment prior to clinical trial. A rapid, sensitive, reversed-phase high-performance liquid chromatographic method employing an internal standard was developed for the detection of ellipticine and its principal metabolite 9-hydroxyellipticine after extraction from biological samples. The method was successfully applied to the quantitation of ellipticine in mouse blood and tissues after intravenous administration of ellipticine and to mouse blood levels of drug after oral administration. Similar success was achieved in determinations of ellipticine and 9-hydroxyellipticine in samples of spiked human blood and plasma. Mouse blood ellipticine levels monitored over 3 h after the intravenous administration of drug demonstrated a biphasic decline with a terminal half-life of 52 min.

Alkaloids↗
PubMed1982

The hydrolysis of spirohydantoin mustard.

Spirohydantoin mustard (I) is a rationally designed anti-tumor agent with substantial in vivo activity against intracranially implanted tumors in mice. However, hydrolysis of I was much faster than that of mechlorethamine hydrochloride or melphalan, two parenterally administered mustards. The hydrolysis products of I were identified by GC-MS of their silylated derivatives. The decomposition of I (at 25 degrees in 10% dimethylacetamide at pH 4-6), as monitored by GLC was pseudo first-order. The half-life of I ranged from 20 min at pH 4.0 to 14 min at pH 6.0. Nonionic surfactants enhanced the stability of I, but this effect was diminished at lower pH, presumably due to decreased solubility of I in the micelle as more drug was protonated. Several dilute parenterally suitable solvents exhibited no marked effect on the hydrolysis of I. The drug was most stable in a 10% fat emulsion system where the time for 10% decomposition of I was 49 +/- 5 min. Plots of the concentration of I versus time were linear indicating the disappearance was zero order in the 10% fat emulsion system.

Animals↗
PubMed1982

Dependence of salivary drug concentration on salivary flow rate.

Saliva drug concentrations are a function of the saliva flow rate at which they are collected. Increased saliva flow rate tends to restore the salivary concentration towards the free unbound plasma concentration of drug. For those drugs excluded from the saliva relative to their free plasma concentration, stimulation increases the observed drug levels in the saliva. For those drugs concentrated in the saliva relative to their free plasma concentration, stimulation decreases the observed drug levels in the saliva.

Amitriptyline↗
PubMed1981

Determination of delta 9-tetrahydrocannabinol in pharmaceutical vehicles by high-performance liquid chromatography.

A procedure for the determination of delta 9-tetrahydrocannabinol (delta 9-THC) in the presence of its degradation products in pharmaceutical vehicles by high-performance liquid chromatography (HPLC) is described. The method compares favorably with a standard gas-liquid chromatographic procedure used for the analysis of delta 9-THC in sesame oil USP. The HPLC method is suitable for quantitating delta 9-THC in the presence of several pharmaceutical vehicles and excipients including: sesame oil USP, polyvinylpyrrolidone, Emulphor EL620 and Cremophor EL. Extractions are not required and samples require little preparation. Only the addition of an internal standard in an appropriate solvent is necessary before injection. The procedure has been applied to stability studies of delta 9-THC in various pharmaceutical vehicles.

Chromatography, Gas↗
PubMed1981

Stability of anthracycline antitumor agents in four infusion fluids.

The stabilities of doxorubicin hydrochloride, daunorubicin hydrochloride, zorubicin, and aclacinomycin A hydrochloride were studied in various infusion fluids at ambient temperature. Reversed-phase high-pressure liquid chromatographic procedures developed and used in these studies employed internal standards and readily separated each drug from its degradation products. Dilute solutions of the anthracyclines were prepared by appropriate dilutions of the reconstituted solutions of the formulated products with 5% Dextrose Injection, USP (D5W); 0.9% Sodium Chloride Injection, USP (NS); Lactated Ringer's Injection, USP (LR); and Normosol-R pH 7.4. The stability of the anthracyclines was dependent on the pH of the admixture solution which, in turn, was dependent on infusion fluid composition. Daunorubicin and aclacinomycin A exhibited acceptable stability (equal to 90% of the original concentration) in D5W, NS, and LR for more than 48 hours. Doxorubicin manifested similar stability in the first two fluids. Zorubicin showed similar stability only in Normosol-R pH 7.4 fluid for 22 hours.

Aclarubicin↗
PubMed1979

Application of a simple high-performance liquid chromatographic method for the determination of melphalan in the presence of its hydrolysis products.

A procedure for the separation and quantitation of melphalan (L-PAM) and its hydrolysis products by high-performance liquid chromatography is described. The hydrolysis of L-PAM at 25 +/- 0.1 degrees and 41 +/- 0.1 degrees was studied between pH 3.0 and 9.0. The pattern of hydrolysis suggested that L-PAM decomposes via two consecutive pseudo first-order reactions. Pseudo first-order rate constants (k1) were determined for the disappearance of L-PAM at various pH values in buffered solutions and in a formulated product. At both temperatures L-PAM solutions were found to be most stable at low pH. Chloride ion was found to reduce the rate of hydrolysis.

Chromatography, High Pressure Liquid↗
PubMed1978

Tetracycline. Another example of generic bioinequivalence.

Because of the Food and Drug Administration batch certification assurances, state government systems generally purchase antibiotics from the lowest bidder. A tetracycline hydrochloride tablet purchased in this manner is shown to be inferior to the innovator capsule product.

Biological Availability↗