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Biomedical subjects

G B Holmes

Publications and source records attributed to G B Holmes.

27 records · Page 2Linked to original sources
PubMedDate not supplied

Quantitative determination of phenytoin and phenobarbital in capillary blood by Ames Seralyzer.

We evaluated the use of serum obtained from capillary blood specimens with the Seralyzer ARIS (AMES Division Miles Laboratories) assay for phenytoin (PHT) and phenobarbital (PB). The Ames Seralyzer method is capable of measuring PHT and PB concentrations in 10 microliter of serum. Therefore, it may be used to measure concentrations of these drugs in small blood samples, such as obtained by skin puncture and capillary tube collection. In this study, simultaneous venous and capillary samples were obtained from 90 patients with epilepsy. Seralyzer results were compared with serum values from venous blood determined with a gas chromatographic (GC) method. Comparison of PHT values obtained by Seralyzer (Ys) versus GC by linear regression gave the equation: Ys = 0.36 + 0.88 X (r2 = 0.93, n = 63). The mean difference between the Seralyzer and GC was -0.96 micrograms/ml (p less than 0.001). For PB, the equation was: Ys = -0.53 + 1.07 X (r2 = 0.93, n = 31) with a mean difference of +1.28 micrograms/ml (p = 0.02).

Adolescent↗
PubMedDate not supplied

Felbamate increases phenytoin but decreases carbamazepine concentrations.

Felbamate (FBM), a novel antiepileptic drug, was observed to have opposite effects on the serum concentrations of phenytoin (PHT) and carbamazepine (CBZ). Data from two male subjects who stabilized while they received both PHT and CBZ, with serum concentration fluctuations of less than 20 and 25%, respectively, form the basis of this report. Both patients required a greater than or equal to 20% reduction in PHT dose while receiving 38-40 mg/kg/day of FBM. When FBM was tapered to less than 20 mg/kg/day, a sudden drop in PHT concentrations occurred in both patients. As PHT concentrations rose, CBZ concentrations fell in both patients. The CBZ epoxide to parent ratio increased to 0.46 and 0.39, respectively during FBM treatment. The ratios were 0.18 in both patients when not receiving FBM. CBZ concentrations returned to baseline values after FBM was discontinued. This unusual and unexpected effect of FBM on two standard antiepileptic drugs underscores the need for evaluating pharmacokinetic interactions before major drug trials.

Carbamazepine↗
PubMedDate not supplied

Effect of felbamate on phenytoin and carbamazepine serum concentrations.

Felbamate (FBM) is a novel antiepileptic drug (AED) undergoing clinical trials in the United States. During a double-blind, cross-over clinical trial, patients received concomitant phenytoin (PHT) and carbamazepine (CBZ). Dosages of PHT and CBZ were adjusted to maintain serum concentrations +/- 20 and +/- 25% of baseline values. All patients required a PHT dosage decrease of 10-30% during active FBM treatment to maintain stable concentrations. CBZ serum concentrations decreased significantly in patients receiving active FBM. The mean decrease was 1.3 micrograms/ml and occurred in 30 of 32 patients. Therefore, FBM apparently causes a bidirectional effect on the serum concentrations of PHT and CBZ when all three drugs are taken concomitantly.

Adolescent↗
PubMedDate not supplied

Discontinuation of phenytoin and carbamazepine in patients receiving felbamate.

Five patients participated in a controlled discontinuation of phenytoin (PHT) and carbamazepine (CBZ) after a study in which all subjects had felbamate (FBM) added to both PHT and CBZ. Four subjects (three women and 1 man aged 23-36 years) completed the protocol. Mean total seizure frequency per day with PHT and CBZ was 1.33 +/- 0.93 (mean +/- SEM), decreasing to 0.87 +/- 0.71 with addition of FBM, and 0.82 +/- 0.78 after discontinuation of PHT. Only one subject tolerated discontinuation of CBZ; the other three had dosage reductions of 33, 54, and 63%. Toxicity attributable to FBM was not observed, and patients often described less severe seizures. Results from four refractory patients indicated that FBM was able to replace PHT and reduce the need for CBZ. In addition, as PHT dosages were reduced, FBM clearance decreased 21%. As the CBZ dosages were reduced. FBM clearance decreased an additional 16.5%.

Adult↗
PubMedDate not supplied

Relative bioavailability of rectally administered phenobarbital sodium parenteral solution.

Rectal administration of antiepileptic drugs may be a useful alternative route when oral administration is not possible due to illness, surgery, or status epilepticus. Although parenteral administration often replaces oral administration in these circumstances, there is not always a desirable intravenous line available or repeated intramuscular injections may not be practical. The purpose of this study was to determine the relative bioavailability and time course of absorption of the commercially available parenteral phenobarbital sodium solution administered rectally in comparison with the same preparation given intramuscularly. Seven healthy adult volunteers were given phenobarbital 5 mg/kg intramuscularly and rectally five weeks apart. Eighteen blood samples were drawn over 288 hours. Pharmacokinetic parameters following intramuscular versus rectal administration were the following: area under the curve 5916 vs. 5253 mumol.h/L; half-life 112 vs. 113 h; time to maximum concentration 2.1 vs. 4.4 h; and maximum serum concentration 36.2 vs. 31.4 mumol/L. Mean relative bioavailability for rectal phenobarbital was 90 percent. Therefore, the parenteral phenobarbital sodium solution given rectally is well absorbed and provides a useful alternative route of administration.

Administration, Rectal↗
PubMedDate not supplied

Quantitative determination of intermetatarsal pressure.

Pain, plantar to the metatarsophalangeal joints, is a common location for the presentation of pain in the forefoot. In the absence of fractures or specific inflammatory conditions common causes of pain in this area include: (1) nonspecific metatarsalgia, (2) plantar fat pad atrophy, and (3) interdigital (intermetatarsal) neuroma. The aggravation and possibly the etiology of these forms of forefoot pain may be related to acute or chronic extrinsic pressure to the forefoot. The role of nonweightbearing, compression of the metatarsal heads, weightbearing, and toe-stance (on the metatarsal heads) on the intermetatarsal pressure of the third interspace was measured in eleven asymptomatic volunteers. Intermetatarsal pressures were recorded using the Stryker Miniaturized Digital Fluid Pressure Monitor. Intermetatarsal pressures for nonweightbearing, nonweightbearing with medial-lateral compression of the metatarsal heads, weightbearing, and toe stance averaged 21 mm Hg, 22 mm Hg, 29 mm Hg, and 36 mm Hg, respectively. In comparison to nonweightbearing, significant increases in intermetatarsal pressures were measured with weightbearing (P = .0027) and toe stance (P = .0002). The change noted from weightbearing to toe-stance was also significant (P = .0005). These findings support the proposition that increases in forefoot plantar pressures convey greater pressures to the intermetatarsal space and metatarsal heads. Increased pressures to the intermetatarsal space may likewise lead to or exacerbate the symptoms of patients with fat pad atrophy, nonspecific metatarsalgia and Morton's neuroma.

Adult↗