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Biomedical subjects

K Kushida

Publications and source records attributed to K Kushida.

At least 145 records · Page 8Linked to original sources
PubMed1985

Concurrent determination of valproic acid with other antiepileptic drugs by high-performance liquid chromatography.

We describe a method for the simultaneous determination of valproic acid with four other antiepileptic drugs (phenobarbital, phenytoin, carbamazepine, and primidone) in plasma by high-performance liquid chromatography. These drugs are extracted from plasma by adding a small volume of acetonitrile following saturation with ammonium sulphate. An aliquot of the extract is then injected on a reversed-phase column with a methanol-water mobile phase. The total time required for the whole analytical process including the plasma pretreatment and chromatography is approximately 20 min. The assay method is simple, rapid, reproducible and specific, and considered, therefore, suitable for both emergency and routine uses in monitoring these antiepileptic drugs simultaneously.

Anticonvulsants↗
PubMed1985

Plasma concentrations of lidocaine and its principal metabolites during intermittent epidural anesthesia.

Plasma concentration-time courses of lidocaine and its principal metabolites (monoethylglycinexylidide, MEGX, and glycinexylidide, GX) were studied during intermittent epidural injections of lidocaine HCl in eight female patients (ASA status 1). The initial dose (320-400 mg without epinephrine) followed by top-up injections of about 60% of the mean initial dose every 35-55 min resulted in a plasma accumulation of lidocaine: the peak concentration increased from 2.30 +/- 0.46 (mean +/- SD) microgram/ml following the first injection and 3.34 +/- 0.76 microgram/ml after the second, to 4.11 +/- 0.72 microgram/ml following the third. The maximum concentrations of MEGX and GX were 0.66 +/- 0.22 and 0.28 +/- 0.08 microgram/ml, respectively. A pharmacokinetic model could successfully fit the entire plasma concentration-time profile of lidocaine during repeated epidural injections (r2 = 0.886 to 0.983). Such pharmacokinetic variables as elimination half-life (t1/2, 2.33 +/- 0.43 h), apparent volume of distribution divided by bioavailability (Vd/F, 2.51 +/- 0.61 l/kg), and clearance divided by bioavailability (Cl/F, 11.65 +/- 1.21 ml X kg-1 X min-1) obtained from the female patients were in reasonable agreement with those reported from healthy females receiving the intravenous lidocaine HCl. A computer-aided simulation generated from using the mean kinetic data in a 50-kg woman predicted that plasma lidocaine concentration would reach the postulated toxic range (approximately equal to 6 microgram/ml) after the fourth supplementary dose under a similar dosing scheme as performed in this study. In conclusion, an accumulation of lidocaine in plasma occurs during a usual intermittent epidural dosing.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Simultaneous determination of lidocaine and its principal metabolites by liquid chromatography on silica gel, with aqueous eluent.

We describe the simultaneous determination of lidocaine and its pharmacologically active metabolites, monoethylglycinexylidide and glycinexylidide, in plasma by "high-performance" liquid-chromatography. By use of a bare ( unbonded ) silica gel with aqueous eluents, separations of organic amines such as lidocaine and its metabolites, which are very difficult and have a poor peak symmetry on bonded reversed-phase packings, were easily accomplished with a good peak symmetry. The method is sufficiently precise, sensitive, and specific. Analytical recoveries of all compounds were greater than 90%; CVs for reproducibility were less than 5% for all compounds; the lower detection limits were 0.1 mg/L or less. This method can be used to monitor the concentrations of these compounds in plasma and to prevent the concentration-related side-effect(s).

Adult↗
PubMed1983

Concentration-effect and time-effect relationships of carteolol.

The concentration-beta blocking effect and time-effect relationships of carteolol were examined in eight normal adults given 15 mg i.v. and 20 mg orally on separate occasions. Resting and post-exercise blood pressures and heart rates were assessed before and at various times up to 48 h after each dose. Carteolol, a beta-blocker with some partial agonist activity, produced an insignificant, transient increase in heart rate 2 to 6 h after both doses, and a fall (p less than 0.05) in diastolic blood pressure 4 and 6 h after the intravenous dose and 6 h after the oral dose in the resting supine position, as compared to the corresponding baseline values. All values of the post-exercise heart rate and the double product after each of the doses were significantly (p less than 0.001) below the baseline values for the entire period (48 h) of observation. A significant correlation between the log plasma carteolol concentration (log C) and its beta-blocking effect (E: p less than 0.001, r = 0.508 i.v.; p less than 0.001, r = 0.626, p.o.) was found. The r-values for individuals were higher (0.852 to 0.977, intravenous; 0.817 to 0.981, oral) than for the group as a whole. The slope (m) of the relationship, E = m X log C + r, showed a certain variance within and between individuals.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1983

Pharmacokinetics and absolute bioavailability of carteolol, a new beta-adrenergic receptor blocking agent.

The pharmacokinetics and absolute bioavailability of a new nonselective beta-adrenoreceptor blocking agent, carteolol, were investigated after administration of single intravenous and oral doses to eight normal volunteers. Plasma and urine drug concentrations were measured by an HPLC method. The pharmacokinetic parameters after intravenous dosing were obtained by a two-compartment analysis: elimination or beta-phase t1/2 4.7 +/- 0.3 h; Vc, 0.74 +/- 0.101/kg; Vd, 4.05 +/- 0.48 l/kg; Cl, 10.13 +/- 0.94 ml/min/kg; ClR, 6.56 +/- 0.58 ml/min/kg; and ClNR, 3.57 +/- 0.40 ml/min/kg. The absolute bioavailability obtained from plasma data was 83.7 +/- 8.0%, which was consistent with that derived from analysis of urine of 82.7 +/- 4.2%. The amounts excreted unchanged in urine up to 48 h after the intravenous and oral doses were 65.0 +/- 1.5% and 53.8 +/- 3.2% of the administered doses, respectively. The t1/2 for removal of the drug derived from plasma and urine findings after intravenous and oral dosing were similar, which indicates that the main route of elimination of carteolol is via the kidneys. As the ClR of carteolol exceeded the Cl of creatinine there may be renal tubular secretion of the drug.

Administration, Oral↗
PubMed1983

Simultaneous liquid chromatographic determination of chloramphenicol and antiepileptic drugs (phenobarbital, phenytoin, carbamazepine, and primidone) in plasma.

A method for the simultaneous analysis of chloramphenicol and four antiepileptic drugs (phenobarbital, phenytoin, carbamazepine, and primidone) in plasma by high-performance liquid chromatography (HPLC) is described. The method involves a preliminary extraction of 0.1 ml of plasma with diethyl ether containing phenacetin as an internal standard, chromatography with a reversed-phase column with a methanol-water mobile phase, and detection by measuring ultraviolet absorbance at 210 nm. The method demonstrated sufficient precision, sensitivity, and specificity: the recoveries of the drugs were greater than 95% with the exclusion of primidone (80.3%); the maximum within-day and day-to-day coefficients of variation for all drugs were less than 5%; the lower detection limits were 0.5 microgram/ml or less for all drugs analyzed; and six other antibiotics, phenylethylmalondiamide, carbamazepine-10,11-epoxide, and chloramphenicol esters did not interfere with the analysis. The HPLC method was tested for clinical applicability by analyzing plasma samples from a volunteer who received concurrent single doses of chloramphenicol, phenobarbital, and phenytoin. This method can be used for studying drug interactions between chloramphenicol and antiepileptic drugs and for monitoring the concentrations of these drugs in plasma when administered concurrently, to prevent concentration-related side effect(s) of each drug.

Adult↗
PubMed1981

Immobilization osteoporosis and active vitamin D: effect of active vitamin D analogs on the development of immobilization osteoporosis in rats.

The therapeutic effects of vitamin D analogs, 1,24(R)-dihydroxycholecalciferol [1,24(R)-(OH)2D3], 1,24(S)-dihydroxycholecalciferol [1,24-(S)(OH)2D3], and 1,25-dihydroxycholecalciferol [1,25(OH)2D3] on immobilization osteoporosis were studied in rats. The right hind limb was immobilized through application of a plaster cast following the section of the sciatic nerve. The left hind limb was intact. Vitamin D analogs were orally administered for 6 weeks at dose levels of 0.02 and 0.10 micrograms/kg/day, respectively. The mean lengths of the immobilized femurs were not significantly different from those of the intact femurs in all the experimental groups. In the immobilized femur of animals treated with 1,24(R)(OH)2D3, 0.10 micrograms/kg, dry and ash weights were heavier and calcium and phosphorus contents greater than those in the nontreated group. Furthermore, the amount of calcified bone mass and the cortical thickness of the femurs of the immobilized limb in 1,24(OH)2D3-treated animals were greater than those in the nontreated animals. Treatment with 1,25(OH)2D3 at 0.10 micrograms/kg caused an increase of the bone mass in both immobilized and intact femurs when compared with those of the control group. It was concluded that the administration of 1,24(R)(OH)2D3 diminished the effect of immobilization in the development of osteoporosis without any side effects.

Animals↗
PubMed1979

Effect of 1 alpha-hydroxyvitamin D3 in rats with experimental renal osteodystrophy.

A model of experimental renal osteodystrophy was established in the rats with chronic renal failure induced by partial nephrectomy and therapeutic effects of 1 alpha-hydroxyvitamin D3 (1 alpha-OH-D3) were studied. Male Wistar rats weighing 180 g were 5/6 nephrectomized and fed a normal diet (Ca and P : 1%) for 6 months. After the surgery, serum creatinine levels increased 60% and thereafter continued to rise gradually with their growth for 4 to 5 months, followed by rapid increase. The serum phosphorus levels were also elevated concomitantly and the serum calcium concentrations were normal. Marked bone resorption accompanied with hypertrophy of parathyroid glands was observed by histological examinations (Tetrachrome-Fuchsin stain, contact microradiography and H-E stain). The bone resorption seemed to be due to secondary hyperparathyroidism. Treatment with 0.25 micrograms/kg/day p.o. of 1 alpha-OH-D3 for 10 days in the uremic state resulted in remarkable new bone formation which was confirmed by histological examinations. These results clearly demonstrated that the reduction of nephron mass play a critical clue of renal osteodystrophy and 1 alpha-OH-D3 appears to have a good potential for clinical use in patients with renal failure and metabolic bone diseases.

Animals↗
PubMedDate not supplied

Urinary bone resorption markers in patients with metabolic bone disorders.

Recently, urinary pyridinoline and deoxypyridinoline have been commonly employed as bone resorption markers. We studied these markers in 17 patients with hyperthyroidism, 15 undergoing long-term anticonvulsant drug therapy, and 28 with postmenopausal osteoporosis. Both markers had significantly higher levels than those in age-matched control groups. Values of urinary pyridinoline and deoxypyridinoline correlated well with urinary hydroxyproline levels in patients with hyperthyroidism (r = 0.856, p < 0.001 for pyridinoline and hydroxyproline; r = 0.919, p < 0.001 for deoxypyridinoline and hydroxyproline); however, poor correlations were observed, especially between urinary deoxypyridinoline and urinary hydroxyproline (r = 0.357, NS) in patients with postmenopausal osteoporosis. To compare the discriminatory ability of urinary pyridinoline and deoxypyridinoline, receiver operating characteristic (ROC) curves were generated for each of these patient groups using data from age-matched healthy females as the control group. The areas under the curves for both markers were 100.0% in hyperthyroidism. The areas under the curves for pyridinoline in patients undergoing long-term anticonvulsant drug therapy (mean +/- SE; 98.1 +/- 2.8%) and postmenopausal osteoporosis (77.9 +/- 5.7%) were significantly higher than those for deoxypyridinoline in anticonvulsant drug therapy (92.4 +/- 3.3%) and in osteoporosis (64.9 +/- 4.3%). Using data from premenopausal healthy females as the control group, areas under ROC curves for urinary pyridinoline (100.0%) and deoxypyridinoline (94.8 +/- 5.9%) were significantly higher than those for urinary hydroxyproline (73.8 +/- 9.4%) in patients undergoing long-term anticonvulsant drug therapy. In patients with postmenopausal osteoporosis, those for urinary pyridinoline (97.0 +/- 2.8%) were also significantly higher than those for urinary hydroxyproline (74.0 +/- 6.4%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗