scholarly journals Bioavailability of immediate and controlled release formulations of lithium carbonate

2002 ◽  
Vol 24 (2) ◽  
pp. 74-79 ◽  
Author(s):  
Luciana Vismari ◽  
Maria Laura N Pires ◽  
Ana Amélia Benedito-Silva ◽  
Helena Maria Calil
Keyword(s):  
Single Dose ◽  
Controlled Release ◽  
Lithium Concentration ◽  
Area Under The Curve ◽  
Lithium Carbonate ◽  
Immediate Release ◽  
Dose Administration ◽  
Multiple Doses ◽  
Elimination Half ◽  
Controlled Release Formulations

INTRODUCTION/OBJECTIVES: Controlled-release lithium formulations were developed to minimize elevated blood peaks, related to side-effects and intoxications. However, there is little information about the bioavailability of the only controlled-release lithium formulation available in Brazil. The objective of this study was to compare the bioavailability of controlled-release and immediate-release lithium formulations, after single and multiple doses. METHODS: Twelve healthy volunteers received 900 mg of immediate-release or controlled-release lithium carbonate in single or multiple doses during 9 days. After single dose administration, the following parameters were analyzed for each formulation: maximum lithium concentration (Cmax); time to reach Cmax (t max); area under the curve of serum concentration versus time (AUC0-12 and AUC0-<FONT FACE=Symbol>¥</FONT>) and the elimination half-life (t1/2 elim.). After multiple doses, Cmax; t max; AUC0-12; mean (Cmean) and minimum drug concentration (Cmin) and degree of fluctuation (DF) were analyzed. A 90% confidence interval (90%CI) for the ratio between the AUCs for each formulation was constructed. RESULTS/DISCUSSION: Following single dose, the two formulations were bioequivalent; however, they were not after multiple doses. This fact could be a consequence of methodological limitations of lithium level's measurements since, following single dose, these levels could not be detected at time periods 24 and 48h in many volunteers, compromising the calculation of t1/2 elim ,and consequently of the AUC0<FONT FACE=Symbol>-¥</FONT> and the 90%CI to the ratio of these areas. Therefore, the bioequivalence found after single dose may be an unreliable result.

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.

scholarly journals Compartmental Pharmacokinetics and Tissue Drug Distribution of the Pradimicin Derivative BMS 181184 in Rabbits

1998 ◽  
Vol 42 (10) ◽  
pp. 2700-2705 ◽  
Author(s):  
Andreas H. Groll ◽  
Tin Sein ◽  
Vidas Petraitis ◽  
Ruta Petraitiene ◽  
Diana Callender ◽  
...  
Keyword(s):  
Single Dose ◽  
Half Life ◽  
Peak Plasma ◽  
Volume Of Distribution ◽  
Multiple Dosing ◽  
Time Curve ◽  
Dose Administration ◽  
Single Dose Administration ◽  
Elimination Half ◽  
Dose Dependent

ABSTRACT The pharmacokinetics of the antifungal pradimicin derivative BMS 181184 in plasma of normal, catheterized rabbits were characterized after single and multiple daily intravenous administrations of dosages of 10, 25, 50, or 150 mg/kg of body weight, and drug levels in tissues were assessed after multiple dosing. Concentrations of BMS 181184 were determined by a validated high-performance liquid chromatography method, and plasma data were modeled into a two-compartment open model. Across the investigated dosage range, BMS 181184 demonstrated nonlinear, dose-dependent kinetics with enhanced clearance, reciprocal shortening of elimination half-life, and an apparently expanding volume of distribution with increasing dosage. After single-dose administration, the mean peak plasma BMS 181184 concentration (C max) ranged from 120 μg/ml at 10 mg/kg to 648 μg/ml at 150 mg/kg; the area under the concentration-time curve from 0 to 24 h (AUC0–24) ranged from 726 to 2,130 μg · h/ml, the volume of distribution ranged from 0.397 to 0.799 liter/kg, and the terminal half-life ranged from 4.99 to 2.31 h, respectively (P < 0.005 toP < 0.001). No drug accumulation in plasma occurred after multiple daily dosing at 10, 25, or 50 mg/kg over 15 days, although mean elimination half-lives were slightly longer. Multiple daily dosing at 150 mg/kg was associated with enhanced total clearance and a significant decrease in AUC0–24 below the values obtained at 50 mg/kg (P < 0.01) and after single-dose administration of the same dosage (P < 0.05). Assessment of tissue BMS 181184 concentrations after multiple dosing over 16 days revealed substantial uptake in the lungs, liver, and spleen and, most notably, dose-dependent accumulation of the drug within the kidneys. These findings are indicative of dose- and time-dependent elimination of BMS 181184 from plasma and renal accumulation of the compound after multiple dosing.

scholarly journals PHARMACOKINETIC STUDIES OF A CHRONOTHERAPEUTIC DRUG DELIVERY SYSTEM OF LORNOXICAM BY LC-MS/MS METHOD

2018 ◽  
Vol 10 (6) ◽  
pp. 88
Author(s):  
Sindhu Abraham ◽  
Rajamanickam Deveswaran ◽  
Jayaraman Anbu ◽  
Sharon Furtado ◽  
Bharath Srinivasan
Keyword(s):  
Drug Delivery ◽  
Drug Release ◽  
Maximum Concentration ◽  
Area Under The Curve ◽  
Immediate Release ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Studies ◽  
Elimination Half ◽  
Coated Tablet ◽  
Liquid Chromatography Tandem Mass

Objective: The objective of this study was to investigate differences in pharmacokinetic patterns of immediate release tablet (IR) and compression coated tablet (CCT) of lornoxicam, proposed for the chronotherapeutic treatment of rheumatoid arthritis.Methods: The dosage forms were administered to two groups of white New Zealand rabbits (n=3), and the plasma drug levels were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Pharmacokinetic parameters like maximum concentration (Cmax), time is taken to reach maximum concentration (Tmax), area under the curve (AUC), elimination half-life (t1/2) and Mean Residence Time (MRT) were determined.Results: In the case of IR tablets, the drug was detected within 15 min after oral administration and a Cmax of 1269.57±4.04 ng/ml were attained at 2±0.15 h. With CCT, the drug was detected only after 5 h and a Cmax of 1279.24±12.76 ng/ml were attained at 8±0.10 h. The CCT showed maximum drug release at the eighth hour in comparison to IR tablet which showed maximum release at the second hour of study.Conclusion: The predominant lag time prior to drug release from CCT is an indication that it is consistent with the requirements of chronopharmaceutical drug delivery. The results suggest that the compression coated tablet is a promising approach for chronotherapeutic management of rheumatoid arthritis.

Randomized, double-blind, cross-over trial comparing safety and efficacy of oral controlled-release oxycodone with controlled-release morphine in patients with cancer pain.

1998 ◽  
Vol 16 (10) ◽  
pp. 3222-3229 ◽  
Author(s):  
E Bruera ◽  
M Belzile ◽  
E Pituskin ◽  
R Fainsinger ◽  
A Darke ◽  
...  
Keyword(s):  
Controlled Release ◽  
Cancer Pain ◽  
Treatment Preference ◽  
Dose Ratio ◽  
Double Blind ◽  
Patients With Cancer ◽  
Elimination Half ◽  
Global Ratings ◽  
History Of ◽  
Controlled Release Formulations

PURPOSE Use of oxycodone for chronic cancer pain has been hampered by its short elimination half-life. This study was designed to compare the efficacy and safety of controlled-release formulations of oxycodone and morphine for cancer pain. PATIENTS AND METHODS Thirty-two adult patients with cancer pain and a > or = 3-day history of stable analgesia with oral opioids provided written informed consent and were randomized to controlled-release oxycodone or controlled-release morphine for 7 days. To blind the study using available tablet strengths, the dose ratio of oxycodone to morphine was set at 1:1.5. On day 8, patients were crossed over to the alternate drug for 7 days. Pain intensity was assessed using a visual analog scale (VAS 0 to 100 mm) and a categorical scale (CAT 0 to 4). Side effects were assessed using a checklist (four-point categorical severity) and a nondirected questionnaire. Patients and investigators made blinded global ratings of efficacy and treatment preference. RESULTS Twenty-three patients completed the study (10 men, 13 women). The VAS and CAT scores were (mean+/-SD) 23+/-21 and 1.2+/-0.8 on controlled-release oxycodone, and 24+/-20 (P=.43) and 1.3+/-0.7 (P=.36) on controlled-release morphine. No period or carryover effect was detected. There were no significant differences in adverse effects (P=.40) or ratings of efficacy and preference. The median oxycodone/morphine dose ratio was 1.5 and the maximum was 2.3. CONCLUSION Controlled-release oxycodone is as safe and effective as controlled-release morphine in the treatment of cancer pain.

scholarly journals Comparative Pharmacokinetics of Azithromycin in Serum and White Blood Cells of Healthy Subjects Receiving a Single-Dose Extended-Release Regimen versus a 3-Day Immediate-Release Regimen

2006 ◽  
Vol 51 (1) ◽  
pp. 103-109 ◽  
Author(s):  
Ping Liu ◽  
Hameed Allaudeen ◽  
Richa Chandra ◽  
Kem Phillips ◽  
Arvid Jungnik ◽  
...  
Keyword(s):  
Single Dose ◽  
Blood Cells ◽  
Dose Regimen ◽  
Extended Release ◽  
Drug Exposure ◽  
White Blood Cells ◽  
Area Under The Curve ◽  
Immediate Release ◽  
Mononuclear Leukocytes ◽  
Open Label

ABSTRACT The pharmacokinetic profiles of azithromycin given as a single-dose regimen (2.0-g extended-release microspheres) were characterized in serum and white blood cells (WBC) and compared with those of a 3-day regimen (a 500-mg immediate-release tablet once daily; total dose, 1.5 g) in an open-label, randomized, parallel-group study of 24 healthy adult subjects. Serial blood samples were collected up to 5 days after the start of dosing for both regimens. Safety assessments were conducted throughout the study. A single 2.0-g dose of azithromycin microspheres achieved significantly higher exposures in serum and WBC during the first 24 h after the start of dosing than a 3-day regimen: an approximately threefold higher area under the curve from time zero to 24 h postdose (AUC0-24) and an approximately twofold higher mean peak concentration on day 1. The single-dose regimen provided total azithromycin exposures in serum and WBC similar to those of the 3-day regimen, as evidenced by the similar AUC0-120 and trough azithromycin concentrations in serum and WBC (mononuclear leukocytes [MNL] and polymorphonuclear leukocytes [PMNL]). For both regimens, the average total azithromycin exposures in MNL and PMNL were approximately 300- and 600-fold higher than those in serum. Azithromycin concentrations in MNL and PMNL remained above 10 μg/ml for at least 5 days after the start of dosing for both regimens. This “front-loading” of the dose on day 1 is safely achieved by the extended-release microsphere formulation, which maximizes the drug exposure at the time when the bacterial burden is likely to be highest.

Design and Characterization of Orlistat Bilayered controlled release Tablets

2021 ◽  
pp. 2976-2982
Author(s):  
P. V. Kamala Kumari ◽  
Y. Srinivasa Rao ◽  
S. Akhila ◽  
K. Bhavya Sindhu
Keyword(s):  
Drug Delivery ◽  
Controlled Release ◽  
Half Life ◽  
Therapeutic Index ◽  
Immediate Release ◽  
Dosage Forms ◽  
Control Drug ◽  
Elimination Half ◽  
Biopharmaceutical Properties ◽  
Conventional Dosage

Drug delivery in conventional dosage forms often suffers from the drawbacks of repeated drug administration and large fluctuations in blood drug levels. Controlled drug delivery systems are a convenient way of controlling the dosing frequency responsible for rapid absorption and distribution of drug in conventional dosage forms, and are dependent upon two intrinsic properties of the drug, namely, elimination half-life (t1/2) and therapeutic index (TI). The goal is to give a drug at a sufficient rate, frequency and dose so that the ratio Cmax/Cmin in plasma at steady state is always maintained at effective concentrations during the course of therapy, reducing side effects or improving physicochemical and biopharmaceutical properties. The use of polymers provides the potential to control drug delivery both temporally and spatially. The objective of the present investigation was to develop bilayered tablets of orlistat to achieve controlled release and immediate release. The process is predetermined in such a way to release the drug at an IR and CR by using different polymers. Half life of orlistat is 1-2 hrs, as it has been released immediately. This paper mainly focuses on designing the process to release the drug in a controlled manner by using different polymers like sodium alginate, ethyl cellulose, HPMC.

Sign in / Sign up

Export Citation Format

Share Document