Bioavailability of Paediatric Mixtures Containing Phenoxymethylpenicillin Calcium or Potassium Salt

1982 ◽  
Vol 10 (5) ◽  
pp. 379-382 ◽  
Author(s):  
Kari Soininen ◽  
Hannu Allonen ◽  
Juhani Posti
Keyword(s):  
Potassium Salt ◽  
Calcium Salt ◽  
Healthy Adult ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Salt Mixture ◽  
Time To Peak ◽  
Aqueous Mixture ◽  
The Mean ◽  
Adult Volunteers

The bioavailability of the calcium and potassium salts of Phenoxymethylpenicillin (dose 38,000 I.U./kg) was investigated in eight healthy adult volunteers. Administration of the calcium salt as an aqueous oral mixture resulted in a mean peak plasma concentration of 8·52 mg/l (SD 1·96) and that of the potassium salt mixture in a concentration of 8·40 mg/ml (SD 2·61), p > 0·1. The median time-to-peak levels were 0·75 h and 1·0 h, respectively (p > 0·1). The mean AUC for the calcium salt mixture was 16·94 mg·h/l (SD 3·31) and for the potassium salt 15·84 mg·h/l (SD 4·76), p > 0·09. These findings confirm that an aqueous mixture of calcium phenoxymethylpenicillin is equivalent to a mixture of potassium Phenoxymethylpenicillin.

Psychopharmacology of Attention Deficit Disorder: Pharmacokinetic, Neuroendocrine, and Behavioral Measures Following Acute and Chronic Treatment with Methylphenidate

PEDIATRICS ◽  
1982 ◽  
Vol 69 (6) ◽  
pp. 688-694
Author(s):  
Sally E. Shaywitz ◽  
Robert D. Hunt ◽  
Peter Jatlow ◽  
Donald J. Cohen ◽  
J. Gerald Young ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Attention Deficit ◽  
Attention Deficit Disorder ◽  
Rating Scale ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Area Under The Curve ◽  
Lag Phase ◽  
The Mean ◽  
Mean Concentration

Despite the frequent use of methylphenidate (MPH) in school-aged children with disorders of attention, impulsivity, and activity regulation (attention deficit disorder, ADD), little is known of its clinical pharmacology. The pharmacokinetics of MPH as well as its effects on growth hormone and prolactin were examined after oral administration in 14 boys with ADD ranging in age from 7 to 12 years (mean 10.4 years). Peak concentrations determined in these acute studies were compared with concentrations obtained two hours after MPH administration in another group of children with ADD who were receiving MPH chronically. After a lag phase of approximately ½ to 1 hour, MPH reached a peak plasma concentration at 2.5 ± 0.65 hours after 0.34 mg/kg and 1.9 ± 0.82 hours after 0.65 mg/kg (mean ± SD). Terminal half-lives were 2.53 ± 0.59 and 2.61 ± 0.29 hours after administration of 0.34 and 0.65 mg/kg, respectively. Observed maximal concentrations ranged from 11.2 ± 2.7 ng/ml after administration of 0.34, and 20.2 ± 9.1 ng/ml after administration of 0.65 mg/kg. The mean area under the curve after administration of 0.65 mg/kg was approximately double that calculated at 0.34 mg/kg. Plasma growth hormone increased significantly from an initial (pre-MPH) mean concentration of 4.4 to peak at two hours at 10.5 ng/ml. Prolactin concentration declined significantly from a pre-MPH level of 9.5 to a nadir at 1½ hours of 3.80 ng/ml, supporting the notion that MPH is acting via central dopaminergic mechanisms. MPH concentrations in children receiving doses of 0.34 mg/kg chronically averaged 8.00 ± 0.91 at two hours, after medication, approximating the mean concentration at the same time observed in the acute study. The concentration of MPH in single "spot" samples obtained at two to three hours after administration of medication were significantly correlated with the percentage of improvement in the abbreviated Conners rating scale, indicating a relationship between plasma MPH concentration and clinical response.

Propranolol-Augmented, Exercise-Induced Human Growth Hormone Release

PEDIATRICS ◽  
1975 ◽  
Vol 56 (5) ◽  
pp. 804-807
Author(s):  
Noel Keith Maclaren ◽  
Glen Edward Taylor ◽  
Salvatore Raiti
Keyword(s):  
Conditioned Response ◽  
Healthy Adult ◽  
Human Growth ◽  
Hormone Release ◽  
Fasting Serum ◽  
Normal Children ◽  
Repeat Testing ◽  
The Mean ◽  
Exercise Induced ◽  
Adult Volunteers

Serum growth homone (HGH) responses to 20 minutes of exercise 90 minutes after orally given propranolol (0.5 mg/kg; maximum, 40 mg), were assessed in 15 short but otherwise normal children, in 2 obese teen-agers, in 3 hypopituitary children, and in 8 healthy adult volunteers. In six adults HGH responses to exercise alone were also assessed one week previously. Normal children responded with a peak serum HGH concentration of 10 ng/ml or greater, except one whose peak was 7 ng/ml (normal,7 ng/ml). The obese girls showed smaller responses to exercise with propranolol (ex/prop) (peak HGH, 6 ng/ml), to hypoglycemia, and to levodopa (peak HGH, 7 and 4 ng/ml). The three hypopituitary children did not respond to ex/prop or to two other stimuli. In the volunteer adults, the mean HGH responses were greater to ex/prop than to exercise alone, although two out of six did not have increased levels with exercise. There were also elevations of fasting serum HGH levels before exercise and propranolol on repeat testing. These results suggest that orally given propranolol improves the exercise-HGH stimulation test both in the number of responders and in the degree of response. Some individuals have an anticipatory HGH secretion before exercise due to a conditioned response.

scholarly journals Phase 1 Study of the Safety, Tolerability, and Pharmacokinetics of Vaborbactam and Meropenem Alone and in Combination following Single and Multiple Doses in Healthy Adult Subjects

2018 ◽  
Vol 62 (4) ◽  
Author(s):  
Christopher M. Rubino ◽  
Sujata M. Bhavnani ◽  
Jeffery S. Loutit ◽  
Elizabeth E. Morgan ◽  
Dan White ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Healthy Adult ◽  
Clinical Investigation ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Double Blind Study ◽  
Time Curve ◽  
Time Zero ◽  
Concentration Time ◽  
Plasma Concentration Time Curve

ABSTRACTMeropenem-vaborbactam is a fixed combination of the novel β-lactamase inhibitor vaborbactam and the carbapenem antibiotic meropenem, developed for the treatment of serious infections caused by drug-resistant Gram-negative bacteria. The safety, tolerability, and pharmacokinetics (PK) of vaborbactam and meropenem following single and multiple ascending doses of each study drug administered alone or combined were evaluated in 76 healthy adult subjects in a randomized, placebo-controlled, double-blind study. Subjects were enrolled in 1 of 5 dose cohorts (receiving 250 to 2,000 mg vaborbactam and/or 1,000 to 2,000 mg meropenem) alone or in combination. No subjects discontinued the study due to adverse events (AEs), and no serious AEs were observed. The pharmacokinetics of meropenem and vaborbactam were similar when given alone or in combination; all evaluated plasma PK exposure measures (peak plasma concentration, area under the plasma concentration-time curve [AUC] from time zero to the last measurable concentration area under the plasma concentration-time curve, and AUC from time zero to infinity) were similar for the study drugs alone versus those in combination, indicating no pharmacokinetic interaction between meropenem and vaborbactam. Across all treatments, 47 to 64% of an administered meropenem dose and 75 to 95% of vaborbactam was excreted unchanged in the urine over 48 h postdose. Meropenem and vaborbactam, when given alone or in combination, have similar pharmacokinetic properties, with no plasma or urine PK drug-drug interactions, and are well tolerated. These findings supported further clinical investigation of the combination product. (This study is registered at ClinicalTrials.gov under registration no. NCT01897779.)

Bioavailability of a Combination Preparation of Trimethoprim and Folic Acid

1983 ◽  
Vol 11 (5) ◽  
pp. 294-297
Author(s):  
Kari Soininen ◽  
Terttu Kleimola
Keyword(s):  
Folic Acid ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Significant Rise ◽  
Peroral Administration ◽  
New Type ◽  
Combination Preparation ◽  
Adult Volunteers ◽  
Serum Folic Acid

The bioavailability of folic acid and trimethoprim was investigated from a combination preparation of folic acid (0·25 mg) and trimethoprim (100 mg) in ten healthy adult volunteers. Peroral administration of the preparation resulted in a mean peak plasma concentration of trimethoprim 1·09 mg/l (SEM 0·06). The AUC values for trimethoprim were 12·42 mg.h/l and 12·77 mg.h/l corresponding to combination preparation and plain trimethoprim, p >0·1. After administration 0·25 mg folic acid in the combination preparation, there was a significant rise in serum folic acid concentrations. The AUC from 0–8 hours was 199·8 nmol.h/l (SEM 8·1) and 166·3 nmol.h/l (SEM 14·2) corresponding to combination preparation and plain trimethoprim, p < 0·001. A loading dose of folic acid 10 mg was given intramuscularly 24 hours before drug intake. This new type of formulation of trimethoprim and folic acid has been developed in order to prevent in long-term use the adverse haematological effects induced by trimethoprim alone.

Bioavailability of Temazepam: Comparison of Four 7.5-mg Capsules with a Single 30-mg Capsule

1993 ◽  
Vol 27 (6) ◽  
pp. 695-699 ◽  
Author(s):  
Craig Abolin ◽  
Dar-Shong Hwang ◽  
Frank Mazza
Keyword(s):  
Peak Concentration ◽  
Dosage Form ◽  
Peak Plasma ◽  
Statistical Significance ◽  
Plasma Concentrations ◽  
Latin Square ◽  
Open Label ◽  
Time To Peak ◽  
Rate Of Absorption ◽  
The Mean

OBJECTIVE: To compare the bioavailability of four temazepam 7.5-mg capsules (Restoril, Sandoz Pharmaceuticals) with that of a single temazepam 30-mg capsule. DESIGN: Single-dose, open-label, two-period, crossover (replicated Latin square). SETTING: Domiciled environment for clinical testing. PARTICIPANTS: Twenty-six healthy male volunteers aged 18–40 years; 25 completed the study. INTERVENTIONS: Subjects randomly received either four temazepam 7.5-mg capsules or one temazepam 30-mg capsule. Blood samples were drawn at various time points after each period (0-48 h), and analyzed for plasma concentration of temazepam. The washout period between doses was five days. MAIN OUTCOME MEASUREMENTS: Five parameters of both dosage forms were compared: (1) area under curve (AUC), (2) peak concentration (Cmax), (3) time to peak concentration (Tmax), (4) apparent rate constant for absorption, and (5) lag time for appearance of drug in plasma. Statistical procedures included ANOVA, power analysis, and confidence limits. RESULTS: The mean AUC for the four 7.5-mg capsules and one 30-mg capsule differed by less than 2 percent and the mean Cmax differed by less than 14 percent for the two dosage strengths; neither of these differences reached statistical significance (p>0.05). The 7.5-mg capsules reached peak plasma concentrations significantly faster than the 30-mg dosage form (mean Tmax 1.18 and 1.73 h, respectively; p=0.01). CONCLUSIONS: The two formulations of temazepam were bioequivalent with respect to the extent of bioavailability. Regarding the rate of absorption, however, the 7.5-mg capsules reached peak plasma concentrations significantly faster than the 30-mg dosage form.

Absorption of Penicillin V from Mixture Formulations. Comparison of Potassium and Benzathine Salts

1981 ◽  
Vol 9 (3) ◽  
pp. 189-190 ◽  
Author(s):  
Markku Heikinheimo ◽  
Tapani Hovi
Keyword(s):  
Single Dose ◽  
Serum Level ◽  
Potassium Salt ◽  
Absorption Rate ◽  
Peak Level ◽  
Serum Levels ◽  
Dose Administration ◽  
Level Curves ◽  
The Mean ◽  
Adult Volunteers

The absorption rate and serum level curves of two commercial phenoxymethylpenicillin mixture preparations were compared in adult volunteers. Both the potassium salt (Primcilliri®) and the benzathine salt (V-Pen ped forte®) of V-penicillin were rapidly absorbed and the mean peak serum levels were obtained with both preparations within the first hour after single dose administration. The mean peak level obtained with the potassium salt was several-fold higher (p < 0.001) and was also reached within a shorter time than that of the benzathine preparation. These results confirm the earlier evidence, obtained with other formulae, for the superior bioavailability of the potassium salt of V-penicillin as compared to most other derivatives used in V-penicillin mixtures.

scholarly journals Effects of the Antifungals Voriconazole and Fluconazole on the Pharmacokinetics of S-(+)- and R-(−)-Ibuprofen

2006 ◽  
Vol 50 (6) ◽  
pp. 1967-1972 ◽  
Author(s):  
Ville-Veikko Hynninen ◽  
Klaus T. Olkkola ◽  
Kari Leino ◽  
Stefan Lundgren ◽  
Pertti J. Neuvonen ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Geometric Mean ◽  
Plasma Concentrations ◽  
Time Curve ◽  
Respective Control ◽  
Control Value ◽  
Racemic Ibuprofen ◽  
The Mean

ABSTRACT Our objective was to study the effects of the antifungals voriconazole and fluconazole on the pharmacokinetics of S-(+)- and R-(−)-ibuprofen. Twelve healthy male volunteers took a single oral dose of 400 mg racemic ibuprofen in a randomized order either alone, after ingestion of voriconazole at 400 mg twice daily on the first day and 200 mg twice daily on the second day, or after ingestion of fluconazole at 400 mg on the first day and 200 mg on the second day. Ibuprofen was ingested 1 h after administration of the last dose of voriconazole or fluconazole. Plasma concentrations of S-(+)- and R-(−)-ibuprofen were measured for up to 24 h. In the voriconazole phase, the mean area under the plasma concentration-time curve (AUC) of S-(+)-ibuprofen was 205% (P < 0.001) of the respective control value and the mean peak plasma concentration (C max) was 122% (P < 0.01) of the respective control value. The mean elimination half-life (t 1/2) was prolonged from 2.4 to 3.2 h (P < 0.01) by voriconazole. In the fluconazole phase, the mean AUC of S-(+)-ibuprofen was 183% of the control value (P < 0.001) and its mean C max was 116% of the control value (P < 0.05). The mean t 1/2 of S-(+)-ibuprofen was prolonged from 2.4 to 3.1 h (P < 0.05) by fluconazole. The geometric mean S-(+)-ibuprofen AUC ratios in the voriconazole and fluconazole phases were 2.01 (90% confidence interval [CI], 1.80 to 2.22) and 1.82 (90% CI, 1.72 to 1.91), respectively, i.e., above the bioequivalence acceptance upper limit of 1.25. Voriconazole and fluconazole had only weak effects on the pharmacokinetics of R-(−)-ibuprofen. In conclusion, voriconazole and fluconazole increased the levels of exposure to S-(+)-ibuprofen 2- and 1.8-fold, respectively. This was likely caused by inhibition of the cytochrome P450 2C9-mediated metabolism of S-(+)-ibuprofen. A reduction of the ibuprofen dosage should be considered when ibuprofen is coadministered with voriconazole or fluconazole, especially when the initial ibuprofen dose is high.

scholarly journals Gastric Emptying in the Postpartum Period

1991 ◽  
Vol 19 (4) ◽  
pp. 521-524 ◽  
Author(s):  
T. Gin ◽  
A. M. W. Cho ◽  
J. K. L. Lew ◽  
G. S. N. Lau ◽  
P. M. Yuen ◽  
...  
Keyword(s):  
Gastric Emptying ◽  
Plasma Concentration ◽  
Postpartum Period ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Time To Peak ◽  
Paracetamol Absorption

We measured gastric emptying, using the technique of paracetamol absorption, in eight women on their first and third postpartum day. Gastric emptying was rapid and there was no difference between the first and third day in the time to peak plasma concentration of paracetamol. Six women returned after six weeks for a further study. Gastric emptying was still rapid but the metabolism of paracetamol appeared to be slower than that found during the immediate postpartum period. These findings suggest that fluid fasting guidelines in patients more than one day postpartum need not be different from those in non-pregnant patients.

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