Disposition kinetics of ceftriaxone and determination of its therapeutic dose in dogs

Purpose: To evaluate the disposition kinetics of ceftriaxone (CFZ) in dogs with a view to determining its therapeutic dose and dosing frequency.Methods: Twelve (12) Basenji dogs (n = 4), divided into 3 groups (A, B and C), were used for the study. Ceftriaxone was administered intramuscularly at doses of 12.5, 25, and 50 mg/kg once to groups A, B and C respectively. Plasma CFZ concentration was determined by agar well diffusion assay at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 h post-treatment, and the pharmacokinetic parameters were determined.Results: Intramuscular injection of CFZ to dogs resulted in rapid absorption, distribution and elimination (p < 0.05). The elimination half-life was short and did not change significantly with increase in dose. Serum concentration of CFZ changed significantly (p < 0.05) with increase in dose of CFZ. The maximum serum concentration (Cmax, 15.00 ± 1.18, 141.37 ± 15.87 and 259 ± 5.21 μg/mL) for groups A, B and C respectively were significantly (p < 0.05) different. The steady state CFZ concentrations; 0.94, 8.81 and 16.19 μg/mL for groups A, B and C, respectively, were significantly (p < 0.05) different. However, there was no significant difference in the time to reach steady state concentrations (Tmax, 00±0.021, 4.00±0.10 and 4.30±0.12 for groups A, B and C respectively). The therapeutic dose of CFZ was therefore determined to be 25 – 50 mg/kg every 4 h.Conclusion: Ceftriaxone undergoes rapid elimination in dogs with a short elimination half-life, thus making it an inconvenient prescription for out-patients in veterinary clinics. Keywords: Ceftriaxone, Pharmacokinetic profile, Dogs, Therapeutic dose, Veterinary clinic

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Efficacy and Safety of AVP-21D9, an Anthrax Monoclonal Antibody, in Animal Models and Humans

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02295-13 ◽

2014 ◽

Vol 58 (7) ◽

pp. 3618-3625 ◽

Cited By ~ 10

Author(s):

Nina V. Malkevich ◽

Robert J. Hopkins ◽

Edward Bernton ◽

Gabriel T. Meister ◽

Eric M. Vela ◽

...

Keyword(s):

Monoclonal Antibody ◽

Animal Models ◽

Half Life ◽

Healthy Human ◽

Serious Adverse Events ◽

Maximum Serum ◽

Content Type ◽

Elimination Half Life ◽

Healthy Humans ◽

Elimination Half

ABSTRACTAnthrax is an acute infectious disease caused by the spore-forming bacteriumBacillus anthracis. Timely administration of antibiotics approved for the treatment of anthrax disease may prevent associated morbidity and mortality. However, any delay in initiating antimicrobial therapy may result in increased mortality, as inhalational anthrax progresses rapidly to the toxemic phase of disease. An anthrax antitoxin, AVP-21D9, also known as Thravixa (fully human anthrax monoclonal antibody), is being developed as a therapeutic agent against anthrax toxemia. The efficacy of AVP-21D9 inB. anthracis-infected New Zealand White rabbits and in cynomolgus macaques was evaluated, and its safety and pharmacokinetics were assessed in healthy human volunteers. The estimated mean elimination half-life values of AVP-21D9 in surviving anthrax-challenged rabbits and nonhuman primates (NHPs) ranged from approximately 2 to 4 days and 6 to 11 days, respectively. In healthy humans, the mean elimination half-life was in the range of 20 to 27 days. Dose proportionality was observed for the maximum serum concentration (Cmax) of AVP-21D9 and the area under the concentration-time curve (AUC). In therapeutic efficacy animal models, treatment with AVP-21D9 resulted in survival of up to 92% of the rabbits and up to 67% of the macaques. Single infusions of AVP-21D9 were well tolerated in healthy adult volunteers across all doses evaluated, and no serious adverse events were reported. (This study has been registered at ClinicalTrials.gov under registration no. NCT01202695.)

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Long acting diltiazem tablets

Drug and Therapeutics Bulletin ◽

10.1136/dtb.30.5.20 ◽

1992 ◽

Vol 30 (5) ◽

pp. 20.1-20

Keyword(s):

Steady State ◽

Liver Function ◽

Calcium Channel ◽

Calcium Channel Blocker ◽

Half Life ◽

Channel Blocker ◽

Elimination Half Life ◽

Elimination Half ◽

Long Acting

Diltiazem is a calcium channel blocker used mainly to treat angina.1 Two manufacturers have recently introduced longer acting formulations of diltiazem, to be taken twice instead of three times a day. The elimination half-life of the drug ranges between 2 and 11 hours, longer when renal or liver function is impaired. The dosage patients need therefore varies considerably, and must often be titrated. The long acting tablets act for over 12 hours, so that the drug accumulates to reach a steady state in about 3 days.

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Time to Steady State following a Change in Dosing Rate

DICP ◽

10.1177/106002808902300607 ◽

1989 ◽

Vol 23 (6) ◽

pp. 468-472 ◽

Cited By ~ 2

Author(s):

Richard G. D'Angio ◽

Peter R. Gwilt

Keyword(s):

Steady State ◽

Half Life ◽

Mathematical Proof ◽

The Body ◽

Steady State Concentration ◽

Initial Concentration ◽

Elimination Half Life ◽

Drug Concentrations ◽

Elimination Half ◽

State Concentration

Drugs administered at fixed intervals or by continuous infusion will accumulate in the body until steady state is achieved. The time to a given percentage of the eventual steady-state concentration has previously been considered to be dependent only on the elimination half-life. This is incorrect. Although the rate of drug accumulation in the body is dependent only on the elimination half-life, the time to a given percentage of steady state is dependent on both the elimination half-life of the drug and the initial concentration. This paper presents the mathematical proof of this concept, computer simulations demonstrating the use of these equations, and nomograms for use in clinical practice. The use of this method allows serum drug concentrations to be evaluated earlier than previously predicted after changes in the dosing rate.

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Dose-Ranging Pharmacokinetic Study of Ciprofloxacin after 200-, 300-, and 400-mg Intravenous Doses

Annals of Pharmacotherapy ◽

10.1177/106002809202600101 ◽

1992 ◽

Vol 26 (1) ◽

pp. 8-10 ◽

Cited By ~ 19

Author(s):

David E. Nix ◽

J. Michael Spivey ◽

Allyn Norman ◽

Jerome J. Schentag

Keyword(s):

Steady State ◽

Half Life ◽

Total Body Clearance ◽

Volume Of Distribution ◽

Elimination Half Life ◽

Elimination Half ◽

The Mean ◽

Total Body ◽

Venous Irritation ◽

Body Clearance

OBJECTIVE: To assess the pharmacokinetics and tolerance of ciprofloxacin after the administration of single intravenous doses of 200, 300, and 400 mg. DESIGN: Double-blind, three-period, randomized, crossover trial. SETTING: Private, university-affiliated, hospital-based, clinical research center. PATIENTS: Normal healthy male volunteers, 18–40 years of age. INTERVENTIONS: Subjects received 200-, 300-, and 400-mg single intravenous doses of ciprofloxacin via 30-minute infusions in random sequence. MAIN OUTCOME MEASURES: Serum ciprofloxacin concentrations were determined by HPLC after each dose and the results were used to derive pharmacokinetic parameters. Tolerance was assessed by reported and observed adverse events, urine microscopic examinations for crystals, and examination of intravenous infusion sites. RESULTS: The mean area under the time curve (AUC) values displayed linearity with respect to the administered dose. No statistical differences were observed in total body clearance, steady-state volume of distribution, or elimination half-life with respect to dose administered. The mean total body clearance, steady-state volume of distribution, or elimination half-life ranged from 36 to 41 L/h, 146 to 169 L, and 3.5 to 3.7 h for the 200-, 300-, and 400-mg doses, respectively. Adverse effects, including venous irritation (four subjects) and crystalluria (two subjects), were mild and did not require withdrawal of any subject from the study. CONCLUSIONS: Intravenous ciprofloxacin in doses ranging from 200 to 400 mg demonstrated linear pharmacokinetics. These single doses were well tolerated, although cases of transient venous irritation and crystalluria were observed.

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Steady-State Pharmacokinetics of Oral Ciprofloxacin in Continuous Cycling Peritoneal Dialysis Patients: Brief Report

Peritoneal Dialysis International ◽

10.3747/pdi.2017.00052 ◽

2018 ◽

Vol 38 (1) ◽

pp. 73-76

Author(s):

Colin Lee ◽

Sandra A.N. Walker ◽

Lesley Palmay ◽

Scott E. Walker ◽

Sheldon Tobe ◽

...

Keyword(s):

Peritoneal Dialysis ◽

Steady State ◽

Serum Concentration ◽

Half Life ◽

Dialysis Patients ◽

Maximum Serum ◽

Continuous Cycling Peritoneal Dialysis ◽

Continuous Cycling ◽

Maximum Serum Concentration ◽

Oral Ciprofloxacin

Steady-state pharmacokinetics of oral ciprofloxacin in 3 continuous cycling peritoneal dialysis (CCPD) outpatients given ciprofloxacin 750 mg b.i.d. for 5 doses was determined. Mean steady-state maximum serum concentration and half-life were 4.4 ±1.5 mg/L and 10.3 ± 2.6 hours, respectively. Mean maximum dialysate concentration in the daytime long dwell and overnight continuous cycling dwell were 7.4 ± 1.2 mg/L and 3.3 ± 1.2 mg/L, respectively. Oral ciprofloxacin 750 mg b.i.d. may be reasonable for bloodstream and peritoneal infections caused by susceptible bacteria in CCPD patients.

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Estimation of the Elimination Half-Life of a Drug at Any Serum Concentration When the Kmand Vmaxof the Drug Are Known: Calculations and Validation With Phenytoin

The Journal of Clinical Pharmacology ◽

10.1002/j.1552-4604.1987.tb03022.x ◽

1987 ◽

Vol 27 (4) ◽

pp. 318-320 ◽

Cited By ~ 4

Author(s):

Thomas R. Browne ◽

David J. Greenblatt ◽

James E. Evans ◽

George K. Szabo ◽

Barbara A. Evans ◽

...

Keyword(s):

Serum Concentration ◽

Half Life ◽

Elimination Half Life ◽

Elimination Half

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Bioavailability pharmacokinetics and residues of marbofloxacin in normal and E.coli infected broiler chicken

International Journal of Pharmacology and Toxicology ◽

10.14419/ijpt.v4i2.6504 ◽

2016 ◽

Vol 4 (2) ◽

pp. 144

Author(s):

Ashraf El-Komy ◽

Taha Attia ◽

Amera Abd El Latif ◽

Hanem Fathy

Keyword(s):

Oral Administration ◽

Half Life ◽

Broiler Chickens ◽

Volume Of Distribution ◽

Pharmacokinetic Parameters ◽

Maximum Serum ◽

Elimination Half Life ◽

Elimination Half ◽

Total Body

The pharmacokinetics of marbofloxacin was studied following a single intravenous, oral administration in normal broiler chickens and repeated oral administrations in normal and experimentally E.coli infected broiler chickens. The pharmacokinetic parameters following a single intravenous injection of 2 mg/kg b.wt., revealed that marbofloxacin obeyed a two compartments open model, distribution half-life (t0.5(α)) was 0.25±0.02 h, volume of distribution (Vdss) was 0.76±0.08 L/kg, elimination half-life (t0.5(β)) was 5.43±0.87 h and total body clearance (CLtot) was 0.09±0.002 l/kg/h. Following a single oral administration, marbofloxacin was rapidly and efficiently absorbed through gastrointestinal tract of chickens as the absorption half-life (t0.5 (ab): 0.62±0.02 h). Maximum serum concentration (Cmax) was 1.15±0.01 μg/ml, reached its maximum time (tmax) at 2.53±0.04 h, elimination half-life (t0.5 (el)) was 7.36±0.20 h indicating the tendency of chickens to eliminate marbofloxacin in slow rate. Oral bioavailability was 73.57± 1.90 % indicating good absorption of marbofloxacin after oral administration. Serum concentrations of marbofloxacin following repeated oral administration of 2 mg/kg b.wt. once daily for five consecutive days, peaked 2 hours after each oral dose with lower significant values recorded in experimentally infected broiler chickens than in normal ones. Tissues residues of marbofloxacin in slaughtered normal chickens was highly in those tissues lung, liver, and kidneys in chickens and the chicken must not be slaughtered before 3 days of stopping of drug administration. It was concluded that the in- vitro protein binding was 12.33±0.82%.

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Determinants of mRNA stability in Dictyostelium discoideum amoebae: differences in poly(A) tail length, ribosome loading, and mRNA size cannot account for the heterogeneity of mRNA decay rates.

Molecular and Cellular Biology ◽

10.1128/mcb.8.5.1957 ◽

1988 ◽

Vol 8 (5) ◽

pp. 1957-1969 ◽

Cited By ~ 23

Author(s):

R A Shapiro ◽

D Herrick ◽

R E Manrow ◽

D Blinder ◽

A Jacobson

Keyword(s):

Steady State ◽

Dictyostelium Discoideum ◽

Mrna Decay ◽

Decay Rates ◽

Time Dependent ◽

Translational Efficiency ◽

Cdna Clones ◽

Dependent Manner ◽

Significant Difference ◽

Kinetics Of

As an approach to understanding the structures and mechanisms which determine mRNA decay rates, we have cloned and begun to characterize cDNAs which encode mRNAs representative of the stability extremes in the poly(A)+ RNA population of Dictyostelium discoideum amoebae. The cDNA clones were identified in a screening procedure which was based on the occurrence of poly(A) shortening during mRNA aging. mRNA half-lives were determined by hybridization of poly(A)+ RNA, isolated from cells labeled in a 32PO4 pulse-chase, to dots of excess cloned DNA. Individual mRNAs decayed with unique first-order decay rates ranging from 0.9 to 9.6 h, indicating that the complex decay kinetics of total poly(A)+ RNA in D. discoideum amoebae reflect the sum of the decay rates of individual mRNAs. Using specific probes derived from these cDNA clones, we have compared the sizes, extents of ribosome loading, and poly(A) tail lengths of stable, moderately stable, and unstable mRNAs. We found (i) no correlation between mRNA size and decay rate; (ii) no significant difference in the number of ribosomes per unit length of stable versus unstable mRNAs, and (iii) a general inverse relationship between mRNA decay rates and poly(A) tail lengths. Collectively, these observations indicate that mRNA decay in D. discoideum amoebae cannot be explained in terms of random nucleolytic events. The possibility that specific 3'-structural determinants can confer mRNA instability is suggested by a comparison of the labeling and turnover kinetics of different actin mRNAs. A correlation was observed between the steady-state percentage of a given mRNA found in polysomes and its degree of instability; i.e., unstable mRNAs were more efficiently recruited into polysomes than stable mRNAs. Since stable mRNAs are, on average, "older" than unstable mRNAs, this correlation may reflect a translational role for mRNA modifications that change in a time-dependent manner. Our previous studies have demonstrated both a time-dependent shortening and a possible translational role for the 3' poly(A) tracts of mRNA. We suggest, therefore, that the observed differences in the translational efficiency of stable and unstable mRNAs may, in part, be attributable to differences in steady-state poly(A) tail lengths.

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