Single injection, low volume periocular anesthesia in 1,000 cases.

Periocular anesthesia is a proven alternative to retrobulbar anesthesia. A prospective evaluation of 1,000 cases was done to study the advantages of single point, low volume periocular anesthesia. This method is efficacious and has an excellent safety profile. The small needle length and the low volume of injected anesthetic enhance the safety. Supplemental anesthesia was needed in only 0.2% of cases. Chemosis was noted in 12.7%. In no case did surgery have to be postponed because of anesthesia-related complications. We believe this method is superior to other multipoint high volume methods of periocular anesthesia.

One point low volume peribulbar anaesthesia versus retrobulbar anaesthesia. A prospective clinical trial.

A prospective trial was conducted on 142 patients who underwent cataract surgery, to compare the efficacy of a single point, low volume peribulbar with that of retrobulbar anaesthesia. It was found that peribulbar anaesthesia is as efficacious as retrobulbar anaesthesia without the associated complications. It also avoids the facial block used by most ophthalmologists to supplement a retrobulbar block, thus markedly reducing the post-operative patient discomfort as well as the total volume of anaesthetic used.

Aggressive chemotherapy in endodermal sinus tumor.

Twenty-eight patients with pure or predominantly endodermal sinus tumor were studied for their clinical behavior, relation with serum alpha-fetoprotein (AFP), and response to intensive postoperative combination chemotherapy. Eight percent of the patients were younger than 20 years of age. One patient was a pseudohermaphrodite. Serum AFP was estimated in 17 patients and was elevated in all. Seven patients were treated with adjuvant chemotherapy following surgery with a cisplatin-containing combination. Five patients (71%) are alive and continue to remain free of disease, with a median survival of 28 months after treatment and an overall median survival of 34 months. Two patients treated with adjuvant chemotherapy experienced early recurrence of the disease, which was detected with a rise in serum AFP before the clinical manifestation of recurrence.

Pharmacokinetics of chlorpheniramine after intravenous and oral administration in normal adults.

Plasma and urinary levels of chlorpheniramine (CPM) and its 2 demethylated metabolites were measured by HPLC after i.v. and oral dosing. In 5 mg (maleate) i.v. bolus studies in 2 subjects, plasma CPM levels were fitted to triexponential equations with terminal half-lives (t 1/1) of 23 and 22 h and area of 3.6 and 3.21/kg, respectively. Intravenous data predicted hepatic blood extraction ratios for the 2 subjects to be 0.06 and 0,07, respectively. Absolute bioavailability from oral solution (10 mg) was 59 and 34%, and from tablets (8 mg) 44 and 25%, respectively, indicating extensive gut first-pass metabolism. Mean t 1/2 from 7 oral fasting studies in 5 subjects was 28 h (19-43 h). Mean absorption lag time was 0.7 h (0.4-1.3 h), and mean peak time was 2.8 h (2-4 h). In 2 subjects, 6 mg solutions were given every 12 h for 9 doses; good correlation between single and multiple dose kinetics was found. Significant accumulation was demonstrated in simulation studies with frequent daily dosing. Estimated accumulation ratios vary from 4.1 to 9.4 (mean 6.5). The t 1/2 from urinary data (collected for 12 days) was consistent with plasma data. The above results suggest the need to reexamine the current practice of frequent daily dosing and the use of sustained or controlled release dosage forms of this drug. The possible cause of reduced plasma clearance of CPM in renal patients is discussed.

Compatibility of calcium chloride and calcium gluconate with sodium phosphate in a mixed TPN solution.

The maximum concentrations of phosphate that will remain soluble in a parenteral nutrient solution containing various concentrations of calcium chloride or calcium gluconate were determined. Various concentrations of sodium phosphate were mixed with FreAmine II (McGaw Laboratories), and the resulting solutions were mixed with 50% dextrose solutions containing various concentrations of calcium chloride or calcium gluconate. The final solutions were sealed and stored at 30 degrees C for 24 hours and then were inspected visually for precipitate formation. It was found that higher equivalent concentrations of phosphate are attainable when calcium gluconate, instead of calcium chloride, is used as the calcium source. Factors found to influence the concentrations of calcium and phosphate that are compatible in amino acid solutions are the calcium salt used, temperature and duration of storage, dextrose concentration, amino acid composition, pH, and other additives.

Titratable acidities of crystalline amino acid admixtures.

Titration curves for total parenteral nutrient (TPN) products were developed and used to determine the amount of alkali needed to make various pH changes. Equations and graphs for determining the titratable acidities of TPN solutions are presented. Samples of five crystalline amino acid products and of 1:1 mixtures of the products with 50% dextrose solutions were titrated to pH 7.4 (with a standard sodium bicarbonate solution) or 8.0 (with a standard sodium hydroxide solution). The samples titrated with sodium hydroxide were first adjusted to pH 5.0 with hydrochloric acid. The pH of the sample was measured after each 0.1-ml addition of hydroxide or bicarbonate to develop a titration curve. Titratable acidities for the five crystalline amino acid products varied widely, ranging from 13.4--45.2 meq of hydroxide/liter and from 135--420 meq of bicarbonate/liter. The amino acid/dextrose mixtures had titratable acidities ranging from 7.8--24.8 meq of hydroxide/liter and from 87--226 meq of bicarbonate/liter. The pH titration data can be used as a guide for determining the amount of base to add to TPN solutions to obtain the desired pH.

Chlorpheniramine. II. Effect of the first-pass metabolism on the oral bioavailability in dogs.

The pharmacokinetics of chlorpheniramine has been studied in six dogs by following the time course of plasma concentration of the drug after intravenous and oral administration of its maleate salt in solution form. After intravenous dosing the decline in chlorpheniramine plasma concentration was typically biexponential. The drug distributed rapidly and extensively to the extravascular tissues. The mean distribution phase half-life was 12.5 min, and the mean apparent volume of distribution, Vdb, was 525% of the body weight in four dogs with normal hematocrits. The mean half-life of elimination was 1.7 hr. The percent absolute availability following oral administration of the drug in the aqueous solution form was found to be dose dependent. At 100-mg dose, in six dogs, an average of 36% of the orally administered dose was found to be systemically available. At 50-mg dose, in one of the four dogs studied, no measurable plasma levels of chlorpheniramine were obtained, and the average bioavailability was only 9.4%. The average availability in four dogs at 200-mg dose was 39.4%. Even at 200-mg oral dose, the dogs did not show any signs of sedation and remained alert all through the experiment. Saturable first-pass gut and/or hepatic elimination has been postulated. The possible implications of these findings on the therapeutic effectiveness of the usual dosing regimen of chlorpheniramine in dogs are discussed.

Visual compatibility of 30 additives with a parenteral nutrient solution.

The visual compatibility of 30 drug additives with total parenteral nutrient (TPN) solutions (4.25% amino acids, 25% dextrose injection) was studied. For each drug additive, three TPN solutions were mixed; two were stored for 22 hours at 4 C then allowed to equilibrate to room temperature for two hours. Two 25-ml samples from each TPN solution were examined immediately or after 25 hours for visual appearance, particulate matter levels and pH. A microscope was used to count and measure particles filtered from samples on a 0.8-micrometer filter. Only the TPN solutions containing amphotericin B showed any visual discoloration or precipitation. All amphotericin B samples and the 25-hour ampicillin sodium samples exceeded USP particulate matter specifications. Individual particulate matter levels of the other TPN solutions varied but met USP specifications. With the exception of tetracycline hydrochloride, which dropped the TPN solution's pH 0.9 units, the additives had little effect on pH of the TPN solutions (pH 6.45). Amphotericin B and ampicillin sodium were considered visually incompatible with TPN solutions. All other drug additives tested were visually compatible with TPN solutions.

Chlorpheniramine. I. Rapid quantitative analysis of chlorpheniramine in plasma, saliva and urine by high-performance liquid chromatography.

A method was developed for the rapid quantitative analysis of chlorpheniramine in plasma, saliva and urine using high-performance liquid chromatography. A diethyl ether or hexane extract of the alkalinized biological samples was extracted with dilute acid which was chromatographed on a reversed-phase column using mixtures of acetonitrile and ammonium phosphate buffer as the mobile phase. Ultraviolet absorption at 254 nm was monitored for the detection and brompheniramine was employed as the internal standard for the quantitation. The effects of buffer, pH, and acetonitrile concentration in the mobile phase on the chromatographic separation were investigated. A mobile phase 20% acetonitrile in 0.0075 M phosphate buffer at a flow-rate of 2 ml/min was used for the assays of plasma and saliva samples. A similar mobile phase was used for urine samples. The drug and internal standard were eluted at retention volumes of less than 17 ml. The method can also be used to quantify two metabolites, didesmethyl- and desmethylchlorpheniramine, in the urine. The method can accurately measure chlorpheniramine levels down to 2 ng/ml in plasma or saliva using 1 ml of sample, and should be adequate for biopharmaceutical and pharmacokinetic studies. Various precautions for using the assay are discussed.

Enhancement of dissolution rates of poorly water-soluble drugs by crystallization in aqueous surfactant solutions I: Sulfathiazole, prednisone, and chloramphenicol.

Effects of crystallization of poorly water-soluble drugs in aqueous surfactant solution on in vitro dissolution rates were investigated. Marked enhancement was observed for chloramphenicol, sulfathiazole, and prednisone. Differential thermal analysis studies indicated the presence of small amounts of surfactant in surfactant-treated crystals. Possible mechanisms of dissolution enhancement are discussed.