scholarly journals Comparison of cisplatin-induced nephrotoxicity between single-dose and split-dose administration to rats

2022 ◽  
Vol 147 ◽  
pp. 112619
Author(s):  
Keizo Fukushima ◽  
Azusa Futatsugi ◽  
Maiko Maekawa ◽  
Saya Naito ◽  
Akira Okada ◽  
...  
Keyword(s):  
Single Dose ◽  
Dose Administration ◽  
Split Dose

scholarly journals Pharmacokinetics of Mefloquine Combined with Artesunate in Children with Acute Falciparum Malaria

1999 ◽  
Vol 43 (2) ◽  
pp. 341-346 ◽  
Author(s):  
Ric Price ◽  
Julie A. Simpson ◽  
Paktiya Teja-Isavatharm ◽  
Myint Myint Than ◽  
Christine Luxemburger ◽  
...  
Keyword(s):  
Body Weight ◽  
Single Dose ◽  
Falciparum Malaria ◽  
Multidrug Resistant ◽  
Dose Administration ◽  
Split Dose ◽  
Development Of Resistance ◽  
A Prospective Study ◽  
Cure Rates ◽  
Age And Sex

ABSTRACT Combining artemisinin or a derivative with mefloquine increases cure rates in falciparum malaria patients, reduces transmission, and may slow the development of resistance. The combination of artesunate, given for 3 days, and mefloquine is now the treatment of choice for uncomplicated multidrug-resistant falciparum malaria acquired on the western or eastern borders of Thailand. To optimize mefloquine administration in this combination, a prospective study of mefloquine pharmacokinetics was conducted with 120 children (4 to 15 years old) with acute uncomplicated falciparum malaria, who were divided into four age- and sex-matched groups. The patients all received artesunate (4 mg/kg of body weight/day orally for 3 days and mefloquine as either (i) a single dose (25 mg/kg) on day 2 with food, (ii) a split dose (15 mg/kg on day 2 and 10 mg/kg on day 3) with food, (iii) a single dose (25 mg/kg) on day 0 without food, or (iv) a single dose (25 mg/kg) on day 2 without food. Delaying administration of mefloquine until day 2 was associated with a mean (95% confidence interval) increase in estimated oral bioavailability of 72% (36 to 109%). On day 2 coadministration with food did not increase mefloquine absorption significantly, and there were no significant differences between patients receiving split- and single-dose administration. In combination with artesunate, mefloquine administration should be delayed until the second or third day after presentation.

scholarly journals Bio-Distribution and Pharmacokinetics of Topically Administered γ-Cyclodextrin Based Eye Drops in Rabbits

2021 ◽  
Vol 14 (5) ◽  
pp. 480
Author(s):  
Martin Kallab ◽  
Kornelia Schuetzenberger ◽  
Nikolaus Hommer ◽  
Bhavapriya Jasmin Schäfer ◽  
Doreen Schmidl ◽  
...  
Keyword(s):  
Single Dose ◽  
Drug Concentration ◽  
Vitreous Humor ◽  
Controlled Study ◽  
Eye Drops ◽  
Corneal Tissue ◽  
Single Administration ◽  
Local Tolerability ◽  
Dose Administration ◽  
Retinal Tissue

The purpose of this study was to evaluate the ocular pharmacokinetics, bio-distribution and local tolerability of γ-cyclodextrin (γCD) based irbesartan 1.5% eye drops and candesartan 0.15% eye drops after single and multiple topical administration in rabbit eyes. In this randomized, controlled study, a total number of 59 New Zealand White albino rabbits were consecutively assigned to two study groups. Group 1 (n = 31) received irbesartan 1.5% and group 2 (n = 28) candesartan 0.15% eye drops. In both groups, single dose and multiple administration pharmacokinetic studies were performed. Rabbits were euthanized at five predefined time points after single-dose administration, whereas multiple-dose animals were dosed for 5 days twice-daily and then euthanized 1 h after the last dose administration. Drug concentration was measured by using liquid chromatography-tandem mass spectrometry (LC-MS/MS) in the retinal tissue, vitreous humor, aqueous humor, corneal tissue and in venous blood samples. Pharmacokinetic parameters including maximal drug concentration (Cmax), time of maximal drug concentration (Tmax), half-life and AUC were calculated. To assess local tolerability, six additional rabbits received 1.5% irbesartan eye drops twice daily in one eye for 28 days. Tolerability was assessed using a modified Draize test and corneal sensibility by Cochet Bonnet esthesiometry. Both γCD based eye drops were rapidly absorbed and distributed in the anterior and posterior ocular tissues. Within 0.5 h after single administration, the Cmax of irbesartan and candesartan in retinal tissue was 251 ± 142 ng/g and 63 ± 39 ng/g, respectively. In the vitreous humor, a Cmax of 14 ± 16 ng/g for irbesartan was reached 0.5 h after instillation while Cmax was below 2 ng/g for candesartan. For multiple dosing, the observed Cmean in retinal tissue was 338 ± 124 ng/g for irbesartan and 36 ± 10 ng/g for candesartan, whereas mean vitreous humor concentrations were 13 ± 5 ng/g and <2 ng/g, respectively. The highest plasma concentrations of both irbesartan (Cmax 5.64 ± 4.08 ng/mL) and candesartan (Cmax 4.32 ± 1.04 ng/mL) were reached 0.5 h (Tmax) after single administration. Local tolerability was favorable with no remarkable differences between the treated and the control eyes. These results indicate that irbesartan and candesartan in γCD based nanoparticle eye drops can be delivered to the retinal tissue of the rabbit’s eye in pharmacologically relevant concentrations. Moreover, safety and tolerability profiles appear to be favorable in the rabbit animal model.

scholarly journals Efficacy and Safety of Mizoribine by One Single Dose Administration for Patients with Rheumatoid Arthritis

2010 ◽  
Vol 49 (20) ◽  
pp. 2211-2218 ◽  
Author(s):  
Kunihiro Ichinose ◽  
Tomoki Origuchi ◽  
Shin-ya Kawashiri ◽  
Naoki Iwamoto ◽  
Keita Fujikawa ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Single Dose ◽  
Efficacy And Safety ◽  
Dose Administration ◽  
Single Dose Administration

scholarly journals Pharmacokinetics and Safety of Intravenous Ceftolozane-Tazobactam in Healthy Adult Subjects following Single and Multiple Ascending Doses

2012 ◽  
Vol 56 (6) ◽  
pp. 3086-3091 ◽  
Author(s):  
Benjamin Miller ◽  
Ellie Hershberger ◽  
David Benziger ◽  
MyMy Trinh ◽  
Ian Friedland
Keyword(s):  
Single Dose ◽  
Adverse Events ◽  
Healthy Adult ◽  
Volume Of Distribution ◽  
Dose Administration ◽  
Mean Values ◽  
Multiple Doses ◽  
Dosing Regimens ◽  
Dose Levels ◽  
Dose Limiting Toxicity

ABSTRACTThe pharmacokinetics and safety of ceftolozane, a novel cephalosporin, and tazobactam, a β-lactamase inhibitor, alone and in combination as a 2:1 ratio in single doses of up to 2,000 and 1,000 mg of ceftolozane and tazobactam, respectively, and multiple doses of up to 3,000 and 1,500 mg of ceftolozane and tazobactam, respectively, per day were evaluated in healthy adult subjects. In part 1, groups of six subjects each received single ascending doses of ceftolozane, tazobactam, and ceftolozane-tazobactam in a within-cohort crossover design. In part 2, groups of 5 or 10 subjects each received multiple doses of ceftolozane, tazobactam, or ceftolozane-tazobactam for 10 days. After a single dose of ceftolozane alone, the ranges of mean values for half-life (2.48 to 2.64 h), the total clearance (4.35 to 6.01 liters/h), and the volume of distribution at steady state (11.0 to 14.1 liters) were consistent across dose levels and similar to those observed when ceftolozane was coadministered with tazobactam. Mean values after multiple doses for ceftolozane alone and ceftolozane-tazobactam were similar to those seen following a single dose. The pharmacokinetics of the dosing regimens evaluated were dose proportional and linear. Ceftolozane-tazobactam was well tolerated and systemic adverse events were uncommon. Mild infusion-related adverse events were the most commonly observed following multiple-dose administration. Adverse events were not dose related, and no dose-limiting toxicity was identified.

Biological response genes after single dose administration of interferon β-1b to healthy male volunteers

2008 ◽  
Vol 199 (1-2) ◽  
pp. 115-125 ◽  
Author(s):  
Jan Hilpert ◽  
Johanna M. Beekman ◽  
Susanne Schwenke ◽  
Kristin Kowal ◽  
David Bauer ◽  
...  
Keyword(s):  
Single Dose ◽  
Biological Response ◽  
Healthy Male ◽  
Interferon Β ◽  
Dose Administration ◽  
Single Dose Administration ◽  
Healthy Male Volunteers ◽  
Male Volunteers
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