journal article
LitStream Collection
Home
Dollery, C. T.; Davies, D. S.; Draffan, G. H.; Dargie, H. J.; Dean, C. R.; Reid, J. L.; Clare, R. A.; Murray, S.
doi: 10.1002/cpt197619111pmid: 1245090
A 300‐µg oral dose of clonidine was administered to 5 normal volunteers and measurements of plasma concentration and effects upon blood pressure, heart rate, circulatory reflexes, sedation, and dry mouth were made for the following 8 hr. The plasma concentration rose to a peak of 1.02 ± 0.52 ng/ml (SD) at 90 min andfell with a mean half‐life of 12.7 hr. Blood pressure of the group fell from 111.0/77.0 to 87.2/60.4 after 3 hr and was 95.2/62.2 mm Hg at 8 hr. Heart rate in recumbency was slowed. Marked sedation and a fall in sativary flow followed the same time‐course as the plasma concentration. The cold pressor response was reduced but the Valsalva overshoot was tiftle affected.
Mahler, Donald L.; Forrest, William H.; Brown, Colin R.; Shroff, Phyllis F.; Gordon, H. Earl; Brown, Byron W.; James, Kenneth E.
doi: 10.1002/cpt197619118pmid: 1106936
To establish the relative potency ofnaproxen and aspirinfor oral analgesia, a 4‐point, noncrossover bioassay with placebo control was undertaken with 197 patients. Subjective‐response methods were used to determine two measures of postoperative analgesia over aperiod of 6 hr. With reasonable confidence for an oral analgesic assay, we found 220 mg of naproxen to be equivalent to 600 mg of aspirin for pain relief and 330 mg of naproxen to be equivalent to 600 mg of aspirin for decreased pain intensity.
Conner, James T.; Parson, Narendra; Katz, Ronald L.; Wapner, Susan; Bellville, J. Weldon
doi: 10.1002/cpt197619124pmid: 1170
Lorazepam. a new benzodiazepine. was compared with a standard surgical premedicant. pentobarbital. In a double‐blind study in 128 patients. lorazepam. 2 and 4 mg. and pentobarbital. 50 and 100 mg. were given intravenously in a randomized sequence. Significant differences were noted; lorazepam was found to provide greater sedation. lack of recall, and greater antianxiety effect than pentobarbital. No significant adverse effects were noted following either drug. Vital signs remained stable.
Ueda, Clarence T.; Hirschfeld, David S.; Scheinman, Melvin M.; Rowland, Maleolm; Williamson, Blake J.; Dzindzio, Barry S.
doi: 10.1002/cpt197619130pmid: 1245091
The disposition kinetics of quinidine in 12 hospitalized patients in whom oral quinidine therapy was to be initiated is described. Quinidine in doses of 2.6 to 5.2 mg/kg base were injused intravenously over 22 min. Plasma sampies were collected during and postinfusion for 24 hr and analyzed by a specijic and sensitive assay procedure. In the 12 hr after administration, postinfusion plasma quinidine concentration decay was described by a biexponential equation. Attempts to include the 24‐hr data point in the fitting procedures resulted in poorer agreements between the theoretical and experimental curves. A 2‐compartment open model is proposed to describe the disposition of quinidine. The volume of the central pool (Vc) and steady‐state volume of distribution (Vdss) were 0.91 ± 0.11 L/kg and 3.03 ± 0.25 L/kg, respectively, and indicate that quinidine distribution is predominantly extravascular. Quinidine distribution was quite rapid (t½α = 7.19 ± 0.70 min), while the apparent elimination half‐life (t½ß) was considerably longer, 6.33 ± 0.47 hr. Total body plasma clearance ranged from 1.49 to 7.15 ml/min/kg (mean 4.70) and is primarily associated with nonrenal mechanisms of drug elimination. Urine specimens collected for 48 hr indicated that 17% of the dose is excreted intact and that urinary excretion was essentially complete within 24 hr. Renal clearance (Clr) was 0.80 ± 0.18 ml/min/kg. The study demonstrated that there is substantial interpatient variability with respect to quinidine disposition.
doi: 10.1002/cpt197619137pmid: 1245092
The pharmacokinetics of oral nalidixinic acid (NA, 1 gm 4 times a day) and oxolinic acid (OA, 750 mg 2 times a day) administeredfor 7 days were studied in the same 10 healthy women on the first, third, and seventh days of the treatment. The peak concentrations of NA + OH‐NA (hydroxynalidixinic acid) in serum at 2 to 3 hr were 34 µg/ml (total) and 23 µg/ml (unconjugated) on the first day and nearly two times higher on the third and seventh days; 82% to 85% of these amounts were NA. The protein‐free fraction of NA + OH‐NA was 8.8% to 18.3%. The total concentration of NA + OH‐NA in urine was 1,220 to 2,700 µg/ml, the unconjugated concentration, 250 to 350 µg/ml, and the chemotherapeutically active concentration, 55 to 75 µg/ml. In steady state the 24‐hr recovery of the total drug was 79% of the daily dose. The excretion rate in urine was 591 to 853 mg 16 hr. The OA concentration in serum was very low on the first day of the treatment, but increased to 4‐ to 5‐fold on the third and seventh days: 6.2 to 6.4 µg/ml (total) and 3.3 to 3.6 µg/ml (unconjugated). The protein‐free OA represented 19% to 23% of the total amount. The modest initial serum concentrations of OA were conjirmed by the low urine concentrations on thefirst day. In steady state the OA concentration in urine was 570 µg/ml (total) and 35 µg/ml (unconjugated), and the 24‐hr recovery, 49% and 3%, respectively. The microbiologic assay gave somewhat higher concentrations of the active drug than did the chemical assay. When taken with food, the excretion of OA in urine was retarded by 6 hr but the 48‐hr recovery was not decreased.
Anderson, Karl E.; Alvares, Alvito P.; Sassa, Shigeru; Kappas, Attallah
doi: 10.1002/cpt197619147pmid: 1245093
The mean plasma half‐life (T½) of antipyrine was prolonged (21.69 ± 1.92 hr) in a group of 10 patients with hereditary hepatic porphyria, 8 of whom had acute intermittent porphyria (AIP) confirmed by decreased erythrocyte uroporphyrinogen‐1‐synthetase (URO‐S) activities and 2 of whom had mixed hepatic porphyria, in comparison to the mean of 20 normal control subjects (12.65 ± 0.86 hr, p < 0.01). Antipyrine T½ was especially prolonged in patients with a history of more severe symptoms, but there was no correlation with the degree of elevation in urinary excretion of the porphyrin precursors δ‐aminolevulinic acid (ALA) and porphobilinogen (PBG). In 7 completely latent carriers of the AIP gene deJect who had normal urinary ALA and PBG levels, the elimination rates of antipyrine from plasma were entirely normal. Phenylbutazone T½ were normal in 10 porphyric patients tested. These results demonstrate that the cytochrome P‐450‐dependent enzyme system for oxidizing antipyrine, but not that for phenylbutazone, is impaired in some AIP individuals in whom the gene defect for the disorder is clinically expressed and that this impairment may be related to the severity of the disease. The partial decrease in URO‐S activity characteristic of AIP does not result in a proJound or generalized decrease in hepatic cytochrome P‐450 Junction, however, even when there is sufficient derangement in the hepatic heme biosynthetic pathway to lead to excessive excretion of chemical intermediates in the pathway.
Galeazzi, Renato L.; Sheiner, Lewis B.; Lockwood, Thomas; Benet, Leslie Z.
doi: 10.1002/cpt197619155pmid: 1171
The question of pR or flow dependence for the renal elimination of procainamide (PCA) was studied under 4 conditions in each of 4 subjects. Each subject received 500 mg of PCA intravenously at weekly intervals while in astate of (1) acid load (NR4Cl) and water deprivation, (2) acid load and water excess, (3) alkali load (NaRCO3) and water deprivation, and (4) alkali load and water excess. Plasma and urine were collected at frequent intervals for PCA and N‐acetyl PCA (NAPA) analysis. Urine flow rates varied markedly between the water deprivation and water excess states (approximately 1.2 vs 5 ml/min, respectively), and urine pH varied markedly between the acid and alkali load states (pH = ca 5 vs 8, respectively). Despite this marked variation, there were no signijicant changes in PCA renal clearance or 24‐hr PCA or NAPA excretion. If passive diffusion of PCA were taking place, such flow and pR changes would have caused marked changes in PCA clearance were the pH partition hypothesis true. We therefore conclude that passive diffusion is not an important mechanism in the renal elimination of PCA in man and that there must be tubular secretion. The implication for the clinical use of the drug is that dose adjustments need not be made in response to variations in urine flow and pH.
Peterson, Patti; Gray, Phillip; Tolman, Keith G.
doi: 10.1002/cpt197619163pmid: 173491
The effect of oral vitamin D3 therapy on calcium balance was compared in 18 institutionalized subjects with drug‐induced osteomalacia and in 18 similar subjects without osteomalacia. The subjects with osteomalacia were receiving standard doses of phenytoin and phenobarbital. Diagnosis of osteomalacia was based on low serum calcium and phosphorus, elevated alkaline phosphatase, and appropriate roentgenographic bone changes. The study group achieved positive calcium balance at approximately 975 IU of vitamin D3 per day, while the control group achieved positive calcium balance at approximately 380 IU of vitamin D3 per day. The difference is highly significant (p < 0.001). These data support previous observations that the osteomalacia of patients receiving anticonvulsant drugs is related to the drugs and that these patients require supplemental doses of vitamin D.
Showing 1 to 10 of 16 Articles