PubMed Health⌕ Search

Biomedical subjects

J C Cloyd

Publications and source records attributed to J C Cloyd.

At least 37 records · Page 2Linked to original sources
PubMed1988

Delivery of paraldehyde in 5% dextrose and 0.9% sodium chloride injections through polyvinyl chloride i.v. sets and burettes.

The delivery of paraldehyde in 5% dextrose injection and 0.9% sodium chloride injection was studied, and the potential interaction between paraldehyde and plastic i.v. containers and sets was evaluated. Paraldehyde was mixed with either 5% dextrose injection or 0.9% sodium chloride injection in polyvinyl chloride (PVC) bags to form a 4% solution. The bags were fitted with standard i.v. administration sets or burettes with administration sets. The solutions were allowed to drip through the i.v. sets for six hours at room temperature. Samples were taken from the i.v. bag or burette and from the distal end of the i.v. sets at zero, two, four, and six hours. Paraldehyde concentrations were measured using a stability-indicating gas chromatographic method, and the presence of plasticizers was detected by a scanning ultraviolet spectrophotometer. The cumulative amount of paraldehyde delivered at the end of the administration set at six hours was 84% for 5% dextrose solutions in burettes, and 89% or 90% for all other solutions and i.v. sets. An ultraviolet-light-absorbing substance appeared in some of the samples, although a relationship between the presence of this substance and type of solution, time of sampling, or site of sample did not emerge. Particulate matter appeared after two hours in all burettes. Approximately 10%-16% of paraldehyde in 5% dextrose or 0.9% sodium chloride injection is lost when delivered from PVC i.v. bags through standard i.v. administration sets and burettes over a six-hour period.(ABSTRACT TRUNCATED AT 250 WORDS)

Drug Stability↗
PubMed1987

Effect of progabide on serum phenytoin and carbamazepine concentrations.

Progabide (PGB) is a gamma-aminobutyric acid (GABA)-agonist drug undergoing clinical evaluation for the treatment of spasticity, movement disorders, and epilepsy. Drug interactions were studied during a randomized, double-blind, crossover trial of the efficacy and toxicity of PGB in patients with partial seizures taking phenytoin (PHT) and carbamazepine (CBZ). In twenty-two of 32 patients (69%) receiving PGB, PHT dosage was reduced, while only four patients (12%) had their dosage reduced during placebo treatment (p less than 0.001). Carbamazepine dosage was decreased in five of 32 patients (16%) during the active treatment, while two patients (6%) had a dosage reduction when receiving placebo (p greater than 0.75). The mean PHT concentrations at the end of baseline, PGB, and placebo treatments were significantly different: 17.5, 20.4, and 16.8 mg/L, respectively (p less than 0.05). Nevertheless, careful adjustment of PHT dosage maintained serum concentration within +/- 25% of target values in both the PGB and placebo periods. Among patients who first received PGB and then placebo, PHT concentrations remained elevated relative to dose suggesting that PGB exerts a prolonged effect on PHT disposition. The addition of PGB to regimens including PHT results in a significant increase in serum PHT concentrations. This drug interaction most likely occurs as a result of PGB mediated inhibition of hepatic microsomal enzymes.

Adult↗
PubMed1986

Mannitol pharmacokinetics and serum osmolality in dogs and humans.

The relationship between mannitol pharmacokinetics and changes in serum osmolality were studied in dogs and humans. Four human subjects each received between 0.5 and 0.7 g/kg of mannitol as an i.v. infusion given over 15 min. Intravenous bolus doses of 0.5, 1.0 and 1.5 g/kg were given to each of five animals. Serial determinations of serum osmolality and serum mannitol concentrations were then performed. Mannitol disposition was best described using a biexponential equation and assuming a two-compartment, open model with elimination from the central compartment. For human subjects, the mean (+/- S.D.) distribution half-life was 2.11 +/- 2.67 min and the elimination half-life was 71.15 +/- 27.02 min. The volume of distribution was 0.47 +/- 0.50 liters/kg and total body clearance was 7.15 +/- 10.23 ml X min-1 X kg-1. The disposition of mannitol in dogs is similar to that observed in humans. Mannitol clearance was independent of dose whereas the central compartment volume was significantly larger (P less than .005) in animals receiving the 1.5-g/kg dose. The volume change is probably due to a rapid, uncompensated shift of water from intracellular to extracellular space. There was a strong positive correlation (r = 0.90) between mannitol concentration and serum osmolality changes. However, neither maximum serum mannitol concentration nor maximum serum osmolality increased proportionately with dose. Only the 1.5-g/kg dose produced a sustained elevation of serum osmolality, confirming that larger doses are more likely to result in prolonged hypertonic dehydration.

Adult↗
PubMed1985

Valproic acid pharmacokinetics in children. II. Discontinuation of concomitant antiepileptic drug therapy.

We studied the pharmacokinetics of valproic acid (VPA) in 11 children before and after discontinuance of enzyme-inducing antiepileptic drugs (AEDs). Valproic acid elimination half-life increased from 7.1 to 11.8 hours. Total and intrinsic VPA clearance decreased by approximately 40%. Valproic acid serum protein binding varied among patients from 7 to 23.8%, but was not altered by AEDs. Seizure control was maintained and mental status improved once all other AEDs were withdrawn. After discontinuation of enzyme-inducing AEDs, serum VPA concentrations can be maintained with a lower VPA dosage given less frequently.

Adolescent↗
PubMed1984

Development of tolerance to the side effects of primidone.

Side effects and antiepileptic drug levels were measured during initiation of and chronic treatment with primidone (PRM). A significant change in the toxicity/serum level ratio was observed 6 h after the initial PRM dose. The amount of toxicity manifested by patients receiving PRM as their initial antiepileptic drug was not different from that of those patients previously treated with phenytoin (PHT) or carbamazepine (CBZ). These findings indicate rapid development of functional tolerance to side effects of PRM, which is not altered by previous exposure to PHT or CBZ. Phenobarbital pretreatment appears to produce cross-tolerance to the effects of PRM.

Adult↗
PubMed1983

Bioavailability of rectally administered carbamazepine suspension in dogs.

The relative bioavailability of an investigational carbamazepine suspension was studied following rectal administration in dogs. Doses of carbamazepine, 20 mg/kg, were given to six dogs. The routes of administration were oral tablet, oral suspension, and rectal suspension. There was no significant difference (p greater than 0.05) in total absorption, as indicated by the area under the serum concentration-time curve between the oral and rectal suspensions. The notable differences between the oral suspension and the rectal suspension were in the maximum serum concentration achieved and the time to achieve this maximum serum concentration. This is due to a prolonged absorption of carbamazepine given rectally, which may limit the ability to achieve therapeutic serum concentrations rapidly. Carbamazepine suspension given rectally may be a satisfactory alternative when administration by the oral route is not possible.

Animals↗
PubMed1983

Pharmacokinetics of valproic acid in children: I. Multiple antiepileptic drug therapy.

We studied the pharmacokinetics of valproic acid (VPA) in 37 children who were taking other antiepileptic drugs. Thirteen children were studied both after initial and while on maintenance valproic acid therapy. Significant differences occurred between initial and maintenance therapy in the mean apparent volume of distribution and in apparent VPA clearance, whereas VPA half-life remained relatively constant. Analysis of data in the 13 children studied on two occasions demonstrated wide intrapatient variability of VPA pharmacokinetics. Children taking VPA together with other antiepileptic medications generally require higher doses of VPA given more frequently.

Adolescent↗
PubMed1981

Primidone kinetics: effects of concurrent drugs and duration of therapy.

Primidone (PRM) kinetics was examined in two groups of adult seizure patients: (1) 10 newly diagnosed in whom only PRM was used, the monotherapy (MT) group, and (2) nine in whom PRM was added to other antiepileptics, the combination therapy (CT) group. Time-concentration data were obtained after an initial dose of 250 mg and during subsequent steady-state periods. PRM elimination was slower (p less than 0.05) after the initial dose in MT patients (half-life (t 1/2) = 15.2 hr, apparent clearance = 35 ml/hr/kg) than in CT patients (t 1/2 = 8.3 hr, clearance = 51 ml/hr/kg). PRM metabolites, phenobarbital and phenylethylmalonamide, appeared much earlier in CT patients. Continued PRM exposure in MT patients was accompanied by an increase in apparent clearance in three of seven patients, but no change in four of seven. In four CT patients in whom other antiepileptics were withdrawn there was a decrease in apparent clearance (61.4 to 29.9 ml/hr/kg) no rates in the range of MT patients. PRM kinetics is influenced by concurrent antiepileptic drugs and by duration of PRM therapy.

Adolescent↗
PubMed1981

Bioavailability of rectally administered valproic acid syrup.

The bioavailability of commercially available valproic acid (VPA) syrup was studied following rectal administration in both dogs and children. Six dogs were studied following both oral (PO) and rectal (PR) administration of a dilute VPA syrup given in a dose of 40 mg per kilogram. There was no significant difference (p greater than 0.1) in the area under the serum concentration-time curve (AUC) between the oral (201.1 mg L-1hr) and rectal 219.6mg L-1hr) routes of administration. Four children were given VPA syrup by the rectal route. In three patients on maintenance VPA therapy, absorption following rectal administration was similar to that following oral administration. In a fourth child, VPA serum levels following an initial rectal dose of 20 mg per kilogram reached a maximum of 42 mg per liter 2 hours after the drug was given. These results indicate that the bioavailability of a diluted VPA syrup given rectally is comparable to that following oral administration. Rectal administration of VPA syrup appears to be a satisfactory alternative when the oral route is unavailable.

Animals↗
PubMed1980

Status epilepticus. The role of intravenous phenytoin.

The treatment of status epilepticus can be improved by using recent developments in the pharmacokinetics and method of intravenous (IV) administration of phenytoin sodium. While diazepam, administered IV, remains the drug of choice for the short-term control of seizures associated with compromised respiratory exchange, phenytoin is effective in preventing recurrence of such seizures and in treating most other forms of status epilepticus. A loading dose of 18 mg/kg given by IV infusion in either 0.45% or 0.9% sodium chloride at a rate no greater than 50 mg/min results in therapeutic serum levels for up to 24 hours in most patients. Maintenance therapy with phenytoin should start at 4 to 7 mg/kg/day and be adjusted to both clinical response and serum levels.

Emergencies↗
PubMed1980

Reduced seizure control due to spoiled phenytoin capsules.

Subtherapeutic phenytoin serum levels and loss of seizure control occurred in a 31-year-old man due to decreased bioavailability of oral drug. During storage at extreme temperatures, physical changes of the phenytoin capsule resulted in altered dissolution characteristics so that only 50% dissolution occurred at 180 minutes compared with 95% in 120 minutes for control capsules. Similar changes were produced in fresh capsules within seven days at high temperature and humidity. The affected patient has metabolic responses to phenytoin that produce marked fluctuations in serum levels with changes in dose. Altered phenytoin serum concentrations may occur with minor dose changes in such patients despite good compliance.

Adult↗
PubMed1980

Availability of diazepam from plastic containers.

The effect of plastic intravenous containers and volume-control administration sets on diazepam availability was studied. Solutions of diazepam in dextrose 5% in water and in 0.9% sodium chloride were prepared in plastic burette chambers and polyvinyl chloride (PVC) bags. Diazepam concentration was measured spectrophotometrically for (1) samples taken from the burette chamber and from the end of the administration set, (2) samples prepared in glass beakers and then infused through plastic administration sets with 0.5-micron filters, (3) samples prepared in PVC bags, and (4) sections of the PVC bags and volume-control sets in which diazepam solutions were prepared and infused. Two hours after admixture, diazepam concentration was significantly reduced in the burette chamber (p less than 0.05). Diazepam concentration was reduced by about 55% after infusion through administration sets (p less than 0.0005) and after two hours of storage in PVC bags. About 24% of the diazepam concentration was recovered from the volume-control set (none was detected in the filter) and 49-56% was recovered from the PVC bags. Admixture of diazepam solutions in plastic containers and administration through plastic administration sets will significantly reduce their diazepam concentrations.

Diazepam↗
PubMed1979

Pharmacokinetic properties of thiopental in two patients treated for uncontrollable seizures.

Thiopental was administered for seizure control in 2 patients with uncontrollable seizures. Serum samples were collected from each patient and assayed for thiopental, and the resulting serum concentration--time data were analyzed pharmacokinetically. The biologic half-life in both patients was significantly longer than previously reported values. Based on the limited number of patients studied, it would appear that half-life and volume of distribution increase with the degree of obesity, while clearance remains unchanged. These pharmacokinetic characteristics would be worthy of consideration in cases where there may be prolonged use of thiopental, eg., for the control of uncontrollable seizures.

Adolescent↗
PubMed1978

Concentration-time profile of phenytoin after admixture with small volumes of intravenous fluids.

A study was designed to determine if admixtures with small volumes of four intravenous fluids (0.45% sodium chloride, 0.9% sodium chloride, 5% dextrose in water and lactated Ringer's) maintain their phenytoin concentrations over a suitable period of time to allow intravenous infusion of the drug. Three phenytoin concentrations (4.6 mg/ml, 9.2 mg/ml and 18.4 mg/ml) were prepared by adding a sufficient volume of an i.v. fluid to the appropriate volume (10.0, 20.0 and 40.0 ml) of phenytoin sodium injection (46 mg of phenytoin acid/ml) to produce a total volume of 100 ml. Each admixture was visually inspected for crystallization, the pH of each solution was determined, and the solutions were filtered through a 0.22-micrometer micropore filter. Unfiltered and filtered aliquots of all solutions were collected at 0, 0.25, 0.5, 1, 4, 8 and 24 hours following admixture. Phenytoin concentrations did not decline systematically during this period nor was there a significant difference (p greater than 0.05) between unfiltered and filtered aliquots in any of the solutions studied, except for the 9.2 mg/ml concentration of 5% dextrose in water. The phenytoin concentrations in the 5% dextrose in water and lactated Ringer's solutions showed the greatest variability over the 24-hour period. The pH for all solutions ranged from 10.15 to 11.50. One-half normal saline and normal saline in small volumes appear to be suitable vehicles for intravenous infusion of phenytoin.

Chromatography, Gas↗