Hydrochloric acid for the correction of severe metabolic alkalosis: an alternate approach.
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Alkalosis↗
Biomedical subjects
J C Cloyd
Publications and source records attributed to J C Cloyd.
Acute phenytoin and primidone intoxication: a pharmacokinetic analysis.
Serial plasma levels of phenytoin, primidone, and phenobarbital were determined in a patient following massive overdose of phenytoin and primidone. The patient's neurologic status improved slowly over a period of 10 days and correlated best with the rise and fall of phenytoin plasma concentrations. The pharmacokinetics of all three agents were characterized by nonlinear regression analysis of their respective plasma concentration-time profiles during the elimination phase, followed by analog computer simulations of their entire plasma concentration-time profile closely resembled the observed values. Average values of Km and Vmax obtained from patients undergoing chronic therapy were used in the simulation and appear to adequately describe phenytoin elimination in this overdose situation. The elimination half-lives of primidone and phenobarbital of 6.2 and 83.5 hours, respectively, were within the "normal range" for patients on chronic therapy. Two distinct absorption phases for primidone and three for phenytoin were noted. The marked decrease in the estimated absorption rate constant between phases 1 and 2 for each drug may have been due to slow dissolution of a large congealed mass of phenytoin and primidone in the gut. The analysis of serial plasma samples following a massive overdose is recommended to provide a reliable data base for therapeutic decisions.
Adult↗
Valproic acid pharmacokinetics in children: III. Very high dosage requirements.
Nine children were studied who required very high doses of valproic acid (VPA) (63.6-105 mg/kg/day) in order to achieve VPA serum concentrations between 50-100 micrograms/ml. These nine children had poorly controlled seizures and were receiving other antiepileptic drugs at the time of this study. The children with very high dose requirements were significantly lighter, shorter, and had less body surface area than the control group. Of the pharmacokinetic parameters studied, total and intrinsic clearance, distribution volume, and valproic acid free fraction were significantly increased in the very high dose group. In three patients who were investigated after co-medications were eliminated, clearances and dosage requirements decreased by more than 50%. We concluded that very high VPA dosages are sometimes required to achieve therapeutic serum drug concentrations and that this therapy occasionally improves seizure control. There were no adverse effects of very high dose therapy that required dosage reduction.
Adolescent↗
Home use of rectal diazepam for cluster and prolonged seizures: efficacy, adverse reactions, quality of life, and cost analysis.
From 1982 through 1987, 128 families, who were instructed in the use of rectally administered diazepam (R-DZP) for the treatment of severe epileptic seizures, were surveyed. Sixty-seven families returned questionnaires and met inclusion/exclusion criteria; the results were used to analyze the medical, psychosocial, and economic impact of this program during the first year following instruction. Twenty-six families did not use R-DZP, primarily because of patient improvement. Among families using R-DZP, a total of 428 doses were administered to 41 children. R-DZP was effective in controlling seizures in 85% of patients. Adverse reactions usually were mild, consisting of drowsiness and/or behavioral changes. Compared to the year prior to instruction, emergency room visits decreased in both R-DZP-treated and -nontreated children; however, cost-savings were greater for the R-DZP group ($1,039.00 vs $420.00 per patient per year). Improvements in quality of life associated with the availability of R-DZP were observed by 58% of users and 27% of nonusers which included improved management of their children's seizures, increased flexibility in family activities, and greater peace of mind. R-DZP appears to be a practical method in the effective treatment of severe seizures at home.
Administration, Rectal↗
Relative bioavailability of rectally administered carbamazepine suspension in humans.
The relative bioavailability of an investigational carbamazepine suspension was studied following rectal administration in human volunteers. Carbamazepine, in doses of approximately 6 mg/kg, was given to nine men. 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, maximum serum concentration, and time to achieve maximum serum concentration between the orally-administered tablet and the rectally administered suspension. Orally administered suspension was absorbed more quickly and completely. All volunteers complained of a strong defecatory urge after the suspension was given rectally. The slow absorption after rectal administration precludes the use of this route in status epilepticus; however, it may be a satisfactory alternative for maintenance therapy when administration by the oral route is not possible.
Adult↗
Double-blind withdrawal of phenytoin and carbamazepine in patients treated with progabide for partial seizures.
Of 30 patients who completed a study of progabide (PGB) as an add-on to both phenytoin (PHT) and carbamazepine (CBZ), 11 volunteered for a double-blind withdrawal protocol in which the PHT and CBZ were to be withdrawn. All patients were receiving 24-32 mg/kg/day PGB in combination with PHT and CBZ. Each patient was randomly assigned to withdrawal of either CBZ or PHT in the first block, and then withdrawal from the other in the second block in an attempt to achieve PGB monotherapy. Seizure occurrence was monitored by sequential analysis, and if a significant increase over baseline seizure frequency occurred, the dose of PGB was increased to a maximum of 45 mg/kg/day. If seizure frequency remained above baseline, the drug being withdrawn was added back and an attempt made to withdraw the other. The study was terminated if these adjustments were not successful in decreasing seizure frequency to baseline. At the conclusion of the study, three patients were being treated with PGB and PHT, two with CBZ and PGB, and six with all three. This study demonstrated the applicability of sequential analysis to antiepileptic drug trials.
Adult↗
Progabide-induced changes in carbamazepine metabolism.
Carbamazepine (CBZ) and carbamazepine 10,11 epoxide (CBZ-E) concentrations were measured during a safety and efficacy trial of progabide. The average CBZ and CBZ-E serum concentrations were calculated from serial measurements during placebo and active treatment periods. Significant decreases in CBZ and significant increases in CBZ-E were observed after the first dose of progabide, and these changes persisted during 3 months of active treatment. Ninety-five percent of the patients had increases in the epoxide/CBZ ratio at the end of 3 months of treatment. These changes are consistent with displacement of CBZ from protein binding sites and inhibition of CBZ-E metabolism induced by progabide and are analagous to the interaction between valproate and CBZ.
Adolescent↗
External leakage from feeding gastrostomies in patients receiving valproate sprinkle.
We reviewed the incidence of external leakage from feeding gastrostomies in 8 patients who received valproate sprinkle (VPA-S). We also identified a control group of 31 children with feeding gastrostomies who were also cared for in our clinic, but who did not receive VPA-S. All patients in both groups have had their feeding gastrostomy greater than or equal to 6 months. Four of 8 children who received VPA-S through feeding gastrostomies developed problems with recurrent external leakage. The incidence of external leakage in our control group of children who had not received VPA-S was 2 in 31 (6.4%). We hypothesize that the external leakage is caused by adherence of the undissolved VPA-S particles to the exterior of the tube, preventing close approximation of the tube to the gastrostomy stoma. In most cases, VPA-S could continue to be administered and the problem of leakage reduced if the tubes were more frequently changed and/or a larger size were used. Complications with either leakage or occlusion were noted in all patients with the button feeding tube who had received VPA-S. Because of the especially high complication rate associated with administration of VPA-S in children with the "button" feeding tubes, we discourage VPA-S administration to children with that device.
Age Factors↗