Ticarcillin: Pharmacokinetics in Man According to Different Administration Schedules

1977 ◽  
Vol 5 (5) ◽  
pp. 308-312 ◽  
Author(s):  
A Dalhoff ◽  
D Höffler
Keyword(s):  
Steady State ◽  
Total Dose ◽  
Continuous Infusion ◽  
Intravenous Infusion ◽  
Half Life ◽  
Loading Dose ◽  
Serum Concentrations ◽  
Semisynthetic Penicillin ◽  
Steady State Serum ◽  
Administration Schedules

The pharmacokinetic characteristics of ticarcillin, a semisynthetic penicillin more active than carbenicillin against Pseudomonas, were studied. Following a rapid intravenous infusion of 1 g, 2 g, 5 g and 10 g ticarcillin respectively the serum half-life was 72·4 minutes independent of the dosage administered. If ticarcillin is administered under steady-state conditions, e.g. continuous infusion of either 2 g/hr or 1 g/hr following a loading dose of 1 g (total dose 5 g) the average steady-state serum concentrations are 125 μg/ml and 105 μg/ml respectively.

Phase I study of etoposide with SDZ PSC 833 as a modulator of multidrug resistance in patients with cancer.

1996 ◽  
Vol 14 (2) ◽  
pp. 610-618 ◽  
Author(s):  
D J Boote ◽  
I F Dennis ◽  
P R Twentyman ◽  
R J Osborne ◽  
C Laburte ◽  
...  
Keyword(s):  
Steady State ◽  
Continuous Infusion ◽  
Half Life ◽  
Area Under The Curve ◽  
Maximum Tolerated Dose ◽  
Loading Dose ◽  
Patients With Cancer ◽  
Psc 833 ◽  
Severe Ataxia ◽  
Dose Limiting Toxicity

PURPOSE To determine the maximum-tolerated dose (MTD) and toxicity of PSC 833 infusion administered with etoposide for 5 days in patients with cancer, and to determine the effect of PSC 833 on etoposide pharmacokinetics. PATIENTS AND METHODS Thirty-five patients were entered onto the study, one of whom was ineligible. Etoposide was delivered from day 1 as a 2-hour infusion over 5 consecutive days at a dose of 75 to 100 mg/m2/d. PSC 833 was administered from day 2 as a 2-hour loading dose and as a 5-day continuous infusion. Doses were escalated from 1 to 2 mg/kg (loading dose) and 1 to 15 mg/kg/d (continuous infusion). RESULTS Thirty-four patients were treated with 53 cycles of PSC 833 and etoposide. Steady-state blood PSC 833 levels more than 1,000 ng/mL were achieved in all patients treated at PSC 833 doses > or = 6.6 mg/kg/d by continuous infusion. Myelosuppression was the most common toxicity. The major dose-related toxicity of PSC 833 was reversible hyperbilirubinemia, which occurred in 83% of cycles. The dose-limiting toxicity of PSC 833 was severe ataxia, which occurred in two of nine patients treated at 12 mg/kg/d and in both of the single patients treated at 13.5 and 15 mg/kg/d. PSC 833 concentrations more than 2,000 ng/mL resulted in an increase in etoposide area under the curve (AUC) of 89%, a decrease in etoposide clearance (Cl) of 45%, a decrease in volume of steady-state distribution (Vss) of 41%, and an insignificant increase in alpha half-life (t 1/2 alpha) and significant increase of beta half-life (t 1/2 beta) of 19% and 77%, respectively. CONCLUSION PSC 833 can be administered in combination with etoposide with acceptable toxicity. The recommended continuous infusion dose of PSC 833 for this schedule is 10 mg/kg/d over 5 days. PSC 833 results in an increase in etoposide exposure and etoposide doses should be reduced in patients receiving PSC 833.

Subcutaneous infusion of bleomycin--a practical alternative to intravenous infusion.

1987 ◽  
Vol 5 (4) ◽  
pp. 648-650 ◽  
Author(s):  
V J Harvey ◽  
M L Slevin ◽  
G W Aherne ◽  
P Littleton ◽  
A Johnston ◽  
...  
Keyword(s):  
Continuous Infusion ◽  
Cell Lines ◽  
Intravenous Infusion ◽  
Half Life ◽  
Animal Studies ◽  
Plasma Concentrations ◽  
Area Under The Curve ◽  
Serum Concentrations ◽  
Subcutaneous Infusion ◽  
Specific Radioimmunoassay

The phase specificity and short half-life of bleomycin make it likely that it would be more effective when administered by continuous infusion. This is supported by studies using cell lines, as well as by animal studies and clinical experience in humans. This study was conducted to compare the pharmacokinetics of intravenous (IV) and subcutaneous infusions of bleomycin. The serum concentrations of bleomycin were measured using a sensitive and specific radioimmunoassay. The results demonstrate similar plasma concentrations and area under the curve for both routes. The subcutaneous infusions were well tolerated, without local discomfort or excoriation. Subcutaneous infusion of bleomycin may thus offer a practical alternative to IV infusions and can be administered to patients who are ambulatory and out of hospital.

Relationship of steady-state serum concentrations of amiodarone and desethylamiodarone to therapeutic efficacy and adverse effects

1987 ◽  
Vol 82 (6) ◽  
pp. 1102-1108 ◽  
Author(s):  
Ruth Falik ◽  
Belinda T. Flores ◽  
Leslie Shaw ◽  
Gene A. Gibson ◽  
Mark E. Josephson ◽  
...  
Keyword(s):  
Steady State ◽  
Adverse Effects ◽  
Therapeutic Efficacy ◽  
Serum Concentrations ◽  
Steady State Serum ◽  
Relationship Of

Carbamazepine-Isoniazid Interaction

PEDIATRICS ◽  
1983 ◽  
Vol 71 (1) ◽  
pp. 139-139
Author(s):  
J. M. WRIGHT
Keyword(s):  
Case Report ◽  
Steady State ◽  
Significant Interaction ◽  
Similar Case ◽  
Drug Regimen ◽  
Acetylator Phenotype ◽  
Serum Concentrations ◽  
Slow Acetylator ◽  
Steady State Serum ◽  
Clinically Significant

To the Editor.— The case report of carbamazepine intoxication secondary to isoniazid administration recently described in this journal1 is a clinically significant interaction. I have previously presented2 a similar case in which a patient receiving carbamazepine, valproate, and nitrazepam developed severe carbamazepine intoxication when isoniazid was added to the drug regimen. The patient was determined to have inherited the slow acetylator phenotype. On careful rechallenge, 300 mg of isoniazid increased carbamazepine steady-state serum concentrations by 85% and decreased carbamazepine clearance by 45%.

Continuous infusion high-dose cytosine arabinoside in refractory childhood leukemia.

1984 ◽  
Vol 2 (10) ◽  
pp. 1092-1097 ◽  
Author(s):  
J Ochs ◽  
J A Sinkule ◽  
M K Danks ◽  
A T Look ◽  
W P Bowman ◽  
...  
Keyword(s):  
Steady State ◽  
Continuous Infusion ◽  
Cytosine Arabinoside ◽  
Fungal Infections ◽  
Dosage Level ◽  
High Dose ◽  
Loading Dose ◽  
Rapid Infusion ◽  
Organ Systems ◽  
State Plasma

Ten pediatric patients with refractory leukemia received continuous infusion high-dose cytosine arabinoside (ara-C) according to one of two escalating dosage schedules: (1) a 500-mg/m2 rapid infusion loading dose followed by 3.5 g/m2 per day continuous infusion daily for four consecutive days, or (2) a 600-mg/m2 rapid infusion loading dose followed by 5.0 g/m2 per day continuous infusion daily for four consecutive days. Major toxicity at the lower dosage level was grade IV hematopoietic aplasia of three weeks' duration. At the higher dosage level, there was a prohibitive toxicity in multiple organ systems including transient noncardiogenic pulmonary edema, fungal infections, peritonitis, severe diarrhea, transaminase elevations, and one treatment-related death due to acute renal failure. In contrast to other methods of administration of high-dose ara-C, no CNS toxicity occurred. Oncolytic responses were seen in all patients and two achieved brief, partial remissions. Steady-state plasma ara-C concentrations were 13 to 40 mumol/L at the 3.5-g/m2 dosage level and 10 to 225 mumol/L at the 5-g/m2 dosage level; CSF concentrations at both dosages ranged from 2 to 5 mumol/L. Intracellular levels and ratios of 1-beta-D-arabinofuranosylcytidine-5' triphosphate and endogenous deoxycytidine 5' triphosphate in marrow blasts varied widely at steady state during infusion. No positive correlation existed between steady-state plasma ara-C levels, toxicity, oncolytic effect, or intracellular nucleotide concentration.

Subchronic Toxicity of S-111-S-WB in Sprague Dawley Rats

2010 ◽  
Vol 29 (4) ◽  
pp. 358-371 ◽  
Author(s):  
Jozef J. W. M. Mertens ◽  
Daniel W. Sved ◽  
Gary B. Marit ◽  
Nichole R. Myers ◽  
Phil L. Stetson ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Steady State ◽  
Ammonium Salts ◽  
Serum Concentrations ◽  
Sprague Dawley ◽  
Subchronic Toxicity ◽  
Lower Serum ◽  
Sprague Dawley Rats ◽  
Steady State Serum ◽  
Effect Level

S-111-S-WB, a mixture of perfluoro fatty acid ammonium salts (C6-C13), was administered orally to Crl:CD (SD)IGS-BR rats. Higher hepatic β-oxidation and liver weights with hepatocellular hypertrophy were present at the 0.125 and 0.6 mg/kg/d dosage. The 0.6 mg/kg/d males developed hepatocellular degeneration and necrosis. Lower serum protein and higher bilirubin and BUN were seen in the 0.6 mg/kg/d males and lower globulin and higher alkaline phosphatase in the 0.125 mg/kg/d males and 0.6 mg/kg/d animals. After 2 weeks, serum concentrations of pentadecafluorooctanoic acid (C8), heptadecafluorononanoic acid (C9), perfluoroundecanoic acid (C11), and perfluorotridecanoic acid (C13) were constant for at least 8 hours. After 90 days, only C9 in the 0.025 mg/kg/d females had reached steady state. Serum C8 and C9 concentrations in the males were 10-fold higher than in the females, whereas C11 and C13 were similar for both genders. The main elimination was via the urine for C8 (males) and C9 (females), and via the feces for C11 and C13. The no-observed-effect level (NOEL) was 0.025 mg/kg/d for the males and 0.125 mg/kg/d for the females.

scholarly journals Evaluation by Monte Carlo Simulation of the Pharmacokinetics of Two Doses of Meropenem Administered Intermittently or as a Continuous Infusion in Healthy Volunteers

2005 ◽  
Vol 49 (5) ◽  
pp. 1881-1889 ◽  
Author(s):  
Wolfgang A. Krueger ◽  
Jurgen Bulitta ◽  
Martina Kinzig-Schippers ◽  
Cornelia Landersdorfer ◽  
Ulrike Holzgrabe ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Monte Carlo ◽  
Liquid Chromatography ◽  
Healthy Volunteers ◽  
Continuous Infusion ◽  
Intravenous Infusion ◽  
High Dose ◽  
Loading Dose ◽  
Group A ◽  
Group B

ABSTRACT Meropenem is a broad-spectrum carbapenem antibacterial agent. In order to optimize levels in plasma relative to the MICs, the ideal dose level and dosage regimen need to be determined. The pharmacokinetics of meropenem were studied in two groups, each comprising eight healthy volunteers who received the following doses: 500 mg as an intravenous infusion over 30 min three times a day (t.i.d.) versus a 250-mg loading dose followed by a 1,500 mg continuous infusion over 24 h for group A and 1,000 mg as an intravenous infusion over 30 min t.i.d. versus a 500-mg loading dose followed by a 3,000-mg continuous infusion over 24 h for group B. Meropenem concentrations in plasma and urine were determined by liquid chromatography-mass spectrometry/mass spectrometry and high-performance liquid chromatography with UV detection, respectively. Pharmacokinetic calculations were done by use of a two-compartment open model, and the data were extrapolated by Monte Carlo simulations for 10,000 simulated subjects for pharmacodynamic evaluation. There were no significant differences in total clearance and renal clearance between group A and group B or between the intermittent treatment and the continuous infusion. The analyses of the probability of target attainment by MIC for the high- and low-dose continuous infusions were robust up to MICs of 4 mg/liter and 2 mg/liter, respectively. The corresponding values for intermittent infusions were only 0.5 mg/liter and 0.25 mg/liter. When these observations were correlated with MICs obtained from the MYSTIC database, intermittent infusion results in adequate activity against two of the most common nosocomially acquired pathogens, Klebsiella pneumoniae and Enterobacter cloacae. However, against Pseudomonas aeruginosa, the evaluation shows a clear advantage of high-dose therapy administered as a continuous infusion. We believe that in the empirical therapy situation, the continuous-infusion mode of administration is most worth the extra efforts. We conclude that clinical trials for evaluation of the continuous infusions of meropenem in critically ill patients are warranted.

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