P700The SK channel inhibitor AP30663, converts vernakalant-resistant persistent AF and prevents its reinduction in pigs

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
J G Diness ◽  
J E Kirchhoff ◽  
L Abildgaard ◽  
N Edvardsson ◽  
U S Soerensen ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Adverse Events ◽  
Half Life ◽  
Plasma Concentrations ◽  
Sk Channels ◽  
Elimination Half Life ◽  
Sk Channel ◽  
Molecule Inhibitor ◽  
Elimination Half ◽  
The Right

Abstract Background Small conductance Ca2+-activated K+-channels (SK-channels) are a promising new atrial selective target for treatment of atrial fibrillation (AF). AP30663 is a small molecule inhibitor of SK-channels that is currently undergoing clinical trials for treatment of AF. Here we present preclinical data from conscious pigs with persistent AF treated with AP30663. Purpose To examine the pharmakokintetics (PK) of AP30663 in anaesthetized pigs and to test whether AP30663 could cardiovert AF that was resistant to treatment by 4 mg/kg vernakalant in pigs. Methods A total of 12 Danish landrace pigs (gilts) were used for the experiments (2 for PK and 10 for cardioversion of AF). Ten conscious pigs with implanted neurostimulators were tachypaced in the right atrium for 17±5 days until persistent AF that did not respond to treatment with 4 mg/kg vernakalant was obtained. After 3±2 days of vernakalant-resistant AF, the pigs received an infusion of 20 mg/kg AP30663 over 60 minutes. During the infusion the pigs remained conscious and the ECG was monitored. If AF reverted within this period, burst pacing with 50 Hz was applied thrice. Cardioversion was considered successful if sustained AF was reverted. Protection against reinduction of AF was considered successful if no episodes of AF lasting for more than 10 minutes could be reinduced by burst pacing. Results Six out of ten pigs with vernakalant-resistant AF cardioverted during infusion of 20 mg/kg AP30663 over 60 minutes. Four out of six pigs were protected against re-induction of AF by burst pacing. The average time to cardioversion was 29±18 minutes corresponding to calculated free plasma concentrations of 1.0–1.4 μM AP30663. In all the conscious pigs AP30663 was well tolerated with no adverse events. The maximal plasma concentration (Cmax) of AP30663 observed at the end of infusion was 4532±844 ng/ml corresponding to an unbound concentration of 1.54±0.29 μM. The plasma concentrations during infusion were described well by first-order kinetics with a half-time of 5.2 minutes, whereas the plasma concentrations after infusion followed Michaeilis-Menten kinetics with a fast half-life of 6.8 minutes and a slow half-life of 93.7 minutes. Thus, it seems that there is a fast distribution to other tissues and an elimination half-life of approximately 90 minutes. The plasma concentration during infusion reached 90% of the steady state concentration after 17 minutes. Conclusion In an advanced pig model of persistent AF where clinically relevant doses of vernakalant could no longer convert the AF to SR, AP30663 able to convert the pigs to sinus rhythm and protect against reinduction of AF. No signs of adverse events were observed during or after infusion of AP30663. The SK channel inhibitor AP30663 had a fast distribution and an elimination half-life of approximately 90 minutes. The results support the development of AP30663 for treatment of AF in man.

Lactic Acidosis, Hyperglycaemia and Convulsions following Nalidixic Acid Overdosage

1984 ◽  
Vol 3 (3) ◽  
pp. 239-243 ◽  
Author(s):  
P.J.A. Leslie ◽  
R.J. Cregeen ◽  
A.T. Proudfoot
Keyword(s):  
Plasma Concentration ◽  
Lactic Acidosis ◽  
Nalidixic Acid ◽  
Half Life ◽  
Abnormal Behaviour ◽  
Elimination Half Life ◽  
Elimination Half

1 A woman survived ingestion of 32 g nalidixic acid despite developing lactic acidosis, hyperglycaemia, convulsions and abnormal behaviour. 2 The maximum recorded plasma concentration of nalidixic acid was 185 mg/l and the elimination half-life was 3.2 h. 3 Carboxy-nalidixic acid was demonstrated in the plasma. 4 Previously reported cases of nalidixic acid overdosage are reviewed.

Clarithromycin Elevates the Plasma Concentration of Lenalidomide Via Inhibition of MDR1

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3479-3479 ◽  
Author(s):  
Naoki Takezako ◽  
Masatomo Miura ◽  
Akihisa Nagata ◽  
Naohiro Sekiguchi ◽  
Takenori Niioka ◽  
...  
Keyword(s):  
Small Intestine ◽  
Plasma Concentration ◽  
Blood Concentration ◽  
Half Life ◽  
Maximum Concentration ◽  
The Other ◽  
Efflux Transporter ◽  
Elimination Half Life ◽  
Other Hand ◽  
Elimination Half

Abstract Background: Multiple myeloma is still lethal disease. However, the prognosis of this disease has been improving according to the administration of novel agents. Among of these novel agents, lenalidomide is confirmed the validity of consolidation-maintenance setting by a randomized controlled study. The combination of clarithromycin, lenalidomide and dexamethasone (BiRd) has led to highly durable responses in newly diagnosed myeloma (Rossi A et al 2013). However, mechanism of clarithromycin against myeloma cells is not still clear. It is believed that clarithromycin increases the area under the curve and maximum concentration levels of corticosteroids. On the other hand, clarithromycin has an ability to interact with human MDR1 (ATP-binding Cassette Sub-family B Member 1 (ABCB1), P- glycoprotein). Furthermore, lenalidomide is a substrate of MDR1, a membrane efflux transporter ubiquitously expressed in human tissues, such as the small intestine, whose activity could decrease the bioavailability of lenalidomide. Therefore, we examined whether blood concentration of lenalidomide would change with the existence of clarithromycin. Aim: To investigate whether blood concentration of lenalidomide would change with the existence of clarithromycin. Method: Lenalidomide 15 mg (Revlimid; Celgene Corporation, Tokyo, Japan) was orally administered once daily at 08:00 hours according to the recommendations (day1-21) of a 28-day cycle. Dexamethasone (20mg) was administrated on day 1,8,15, and 22. Orally, from day 8 to 21, Clarithromycin 400mg was administrated twice daily. On day 7and 14 of Bird therapy, whole-blood samples were collected just before oral lenalidomide administration, and at 1, 2, 4, and 6 hours thereafter. Pharmacokinetic analysis of lenalidomide was carried out using the standard non-compartmental method using WinNonlin (version 5.2; Pharsight Co, Mountain View, CA). The elimination half-life was calculated from the log-linear regression of the terminal phase of the concentration–time curve using at least 3 sampling points (elimination half-life = ln2/ke; ke = elimination rate constant). The total AUC was calculated using the linear trapezoidal rule. Results: Twenty five patients, who were obtained written informed consent, were enrolled in this study from April 2012 to June 2014. Mean plasma lenalidomide concentrations are shown in Figure 1. According to administration of clarithromycin, plasma concentrations of lenalidomide elevated at 2, 3, and 4 hour, respectably (p=0.045, p=0.039, p=0.042). Furthermore, baseline plasma concentration of lenalidomide was not affected by administration of clarithromycin (p=0.132). On the other hand, AUC24 were not affected by addition of clarithromycin (p=0.213) (Figure 2). In some patients, blood concentration of lenalidomide extremely increased administration of clarithromycin. These patients had wild type of ABCB1, C3435T genotype (C/C) (p=0.036). The other patients who were moderate affected to clarithromycin administration were mutated types (C/T or T/T). Nineteen patients obtained at least VGPR (sCR (9), VGPR (10)). The major adverse event (AE) was skin rush; however, it was manageable, except one patient (Grade 3). Hematological AEs were well tolerable (i.e. Grade 1 or 2, thrombocytopenia). No patient died during BiRd therapy. Discussion: In MM-001 trial, lenalidomide led anti-MM response according to dose dependent manner (Richardson P, et al. 2002). In addition, hematological AEs, especially thrombocytopenia were significant related to AUC24 (p<0.001). Our trial revealed that administration of clarithromycin led to elevate the maximum concentration of lenalidomide acceding to raising the absorption via inhibition of MDR1. On the other hand, administration of clarithromycin did not affect to the baseline plasma concentration of lenalidomide, so we considered that administration of clarithromycin did not affect to renal excretion. For this reason, if the renal function was sufficient, lenalidomide was excreted immediately to urine, so, AUC24 might not rise and toxicities might be tolerable. In conclusion, clarithromycin inhibits MDR1 which is a membrane efflux transporter expressed in the small intestine and raise absorption of lenalidomide. Further studies are warranted. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

Stimulants and Dopamine Augmenters

2008 ◽  
Author(s):  
Chiadi U. Onyike
Keyword(s):  
Half Life ◽  
Plasma Concentrations ◽  
Drug Induced ◽  
Elimination Half Life ◽  
Positive Effects ◽  
Elimination Half ◽  
Ritalinic Acid ◽  
Norepinephrine Reuptake Inhibitor ◽  
Ventrolateral Preoptic Nucleus ◽  
Norepinephrine Reuptake

Stimulants are typically prescribed for their positive effects on mood, motivation, alertness, arousal, and energy. They are believed to exert their pharmacologic effects by increasing synaptic release of endogenous catecholamines (norepinephrine and dopamine) while simultaneously blocking catecholamine reuptake at the nerve terminals. Themost commonly used ‘‘traditional’’ agents are methylphenidate and dextroamphetamine. Methylphenidate reaches peak blood levels in 1 to 3 hours and has an elimination half-life of 2 to 3 hours. Dextroamphetamine reaches peak levels in 2 to 4 hours and has an elimination half-life of 3 to 6 hours. Controlled-release formulations are available, allowing for dosing once daily. Dextroamphetamine is excreted primarily in the urine in unchanged form, whereas methylphenidate is excreted mainly as ritalinic acid. The newer generation stimulant modafinil has been marketed in the United States since 1998. Initially used in the treatment of narcolepsy, it is now prescribed for a wider range of conditions because of its positive effects on wakefulness, vigilance, cognitive performance, and mood. Its pharmacologic effects are thought to result primarily from the stimulation of wakefulness-promoting orexinergic neurons in the anterior hypothalamus. Inhibition of norepinephrine reuptake in the ventrolateral preoptic nucleus and of dopamine reuptake (by binding to the transporter) may contribute to its action. Modafinil is administered orally, achieves peak plasma concentrations in 2 to 4 hours, and has an elimination half-life of 12 to 15 hours. It is 90% metabolized in the liver, and its metabolites are excreted in the urine. The ergot alkaloids bromocriptine and pergolide are familiar to most neurologists in their use in the treatment of Parkinson’s disease (PD) and migraine headache. These dopamine receptor agonists are also used in neuropsychiatry in the treatment of apathetic states in patients recovering from brain trauma, cerebral anoxia, and strokes. Amantadine is another familiar agent used in the treatment of PD and drug-induced parkinsonism. In addition to other effects in the central nervous system (CNS), amantadine facilitates dopamine release and inhibits its reuptake. It thus has modest ‘‘stimulant-like’’ effects useful in the treatment of executive dysfunction syndromes, particularly in patients with dementia. Bupropion is a dopamine and norepinephrine reuptake inhibitor. It usually is prescribed as a ‘‘nonsedating’’ antidepressant, but its potentiation of catecholamine neurotransmission results in modest stimulant-like clinical effects.

scholarly journals Single Intravenous Dose of Oritavancin for Treatment of Acute Skin and Skin Structure Infections Caused by Gram-Positive Bacteria: Summary of Safety Analysis from the Phase 3 SOLO Studies

2018 ◽  
Vol 62 (4) ◽  
pp. e01919-17 ◽  
Author(s):  
G. Ralph Corey ◽  
Jeffery Loutit ◽  
Greg Moeck ◽  
Matthew Wikler ◽  
Michael N. Dudley ◽  
...  
Keyword(s):  
Adverse Events ◽  
Bactericidal Activity ◽  
Half Life ◽  
Safety Data ◽  
Safety Analysis ◽  
Gram Positive ◽  
Serious Adverse Events ◽  
Skin Structure ◽  
Elimination Half Life ◽  
Elimination Half

ABSTRACT Oritavancin is a lipoglycopeptide with bactericidal activity against Gram-positive organisms. Its rapid concentration-dependent bactericidal activity and long elimination half-life allow single-dose treatment of acute bacterial skin and skin structure infections (ABSSSI). SOLO I and SOLO II were randomized, double-blind studies evaluating the efficacy and safety of a single 1,200-mg intravenous (i.v.) dose of oritavancin versus twice-daily i.v. vancomycin for 7 to 10 days in ABSSSI patients. Safety data from both studies were pooled for safety analysis. The database comprised pooled safety data for 976 oritavancin-treated patients and 983 vancomycin-treated patients. The incidences of adverse events, serious adverse events, and discontinuations due to adverse events were similar for oritavancin (55.3, 5.8, and 3.7%, respectively) and vancomycin (56.9, 5.9, and 4.2%, respectively). The median time to onset (3.8 days versus 3.1 days, respectively) and the duration (3.0 days for both groups) of adverse events were also similar between the two groups. The most frequently reported events were nausea, headache, and vomiting. Greater than 90% of all events were mild or moderate in severity. There were slightly more infections and infestations, abscesses or cellulitis, and hepatic and cardiac adverse events in the oritavancin group; however, more than 80% of these events were mild or moderate. Subgroup analyses did not identify clinically meaningful differences in the incidence of adverse events attributed to oritavancin. A single 1,200-mg dose of oritavancin was well tolerated and had a safety profile similar to that of twice-daily vancomycin. The long elimination half-life of oritavancin compared to that of vancomycin did not result in a clinically meaningful delay to the onset or prolongation of adverse events. (This study has been registered at ClinicalTrials.gov under registration no. NCT01252719 and NCT01252732.)

scholarly journals Pharmacokinetics of First-Line Tuberculosis Drugs in Tanzanian Patients

2013 ◽  
Vol 57 (7) ◽  
pp. 3208-3213 ◽  
Author(s):  
Alma Tostmann ◽  
Charles M. Mtabho ◽  
Hadija H. Semvua ◽  
Jossy van den Boogaard ◽  
Gibson S. Kibiki ◽  
...  
Keyword(s):  
Half Life ◽  
Reference Range ◽  
Plasma Concentrations ◽  
Metabolic Ratio ◽  
Drug Intake ◽  
First Line ◽  
Elimination Half Life ◽  
Drug Concentrations ◽  
Elimination Half ◽  
Incidence And Mortality

ABSTRACTEast Africa has a high tuberculosis (TB) incidence and mortality, yet there are very limited data on exposure to TB drugs in patients from this region. We therefore determined the pharmacokinetic characteristics of first-line TB drugs in Tanzanian patients using intensive pharmacokinetic sampling. In 20 adult TB patients, plasma concentrations were determined just before and at 1, 2, 3, 4, 6, 8, 10, and 24 h after observed drug intake with food to estimate the areas under the curve from 0 to 24 h (AUC0–24) and peak plasma concentrations (Cmax) of isoniazid, rifampin, pyrazinamide, and ethambutol. Acetylator status for isoniazid was assessed phenotypically using the isoniazid elimination half-life and the acetylisoniazid/isoniazid metabolic ratio at 3 h postdose. The geometric mean AUC0–24s were as follows: isoniazid, 11.0 h · mg/liter; rifampin, 39.9 h · mg/liter; pyrazinamide, 344 h · mg/liter; and ethambutol, 20.2 h · mg/liter. TheCmaxwas below the reference range for isoniazid in 10/19 patients and for rifampin in 7/20 patients. In none of the patients were theCmaxs for pyrazinamide and ethambutol below the reference range. Elimination half-life and metabolic ratio of isoniazid gave discordant phenotyping results in only 2/19 patients. A substantial proportion of patients had an isoniazid and/or rifampinCmaxbelow the reference range. Intake of TB drugs with food may partly explain these low drug levels, but such a drug intake reflects common practice. The finding of low TB drug concentrations is concerning because low concentrations have been associated with worse treatment outcome in several other studies.

scholarly journals Effects of Single and Repeated Doses on Disposition and Kinetics of Doxycycline Hyclate in Goats

Animals ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 1088 ◽  
Author(s):  
Erdinc Turk ◽  
Orhan Corum ◽  
Ibrahim Ozan Tekeli ◽  
Fatih Sakin ◽  
Kamil Uney
Keyword(s):  
Oral Administration ◽  
Half Life ◽  
Plasma Concentrations ◽  
Wide Distribution ◽  
Drug Dosage ◽  
Oral Route ◽  
Doxycycline Hyclate ◽  
Elimination Half Life ◽  
Elimination Half ◽  
Pharmacokinetic Properties

The aims of this study in goats were to determine the pharmacokinetics of doxycycline hyclate following single intravenous (IV), intramuscular (IM) and oral administrations of 20 mg/kg and to evaluate the pharmacokinetics and accumulation of doxycycline hyclate after repeated oral administrations at a 20 mg/kg dose every 24 h for 5 days. Six healthy male goats were used for the study. The study was performed in four periods according to a longitudinal study with a 15-day washout period. Plasma concentrations of doxycycline were determined using HPLC-UV and analyzed by a non-compartmental method. IM injection of doxycycline caused swelling and pain due to irritation in the injection site. After IM and oral administrations, terminal elimination half-life (t1/2λz) and mean residence time (MRT) were prolonged and areas under the curve (AUCs) were low. The mean bioavailability of IM and oral administration was 51.51% and 31.39%, respectively. Following repeated oral administration, the accumulation ratio of doxycycline was 1.76. Pharmacokinetic properties including weak accumulation, wide distribution volume and long elimination half-life can make doxycycline hyclate valuable for repeated use via an oral route in the treatment of some infectious diseases in goats. However, the determination of pharmacodynamic effects on susceptible pathogens isolated from goats is also necessary to confirm the drug dosage regimen.

Buccal Absorption of Fentanyl Is pH-Dependent in Dogs 

1995 ◽  
Vol 82 (3) ◽  
pp. 759-764 ◽  
Author(s):  
James B Streisand ◽  
Jie Zhang ◽  
Suyi Niu ◽  
Scott McJames ◽  
Remco Natte ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Buccal Mucosa ◽  
Half Life ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Elimination Half Life ◽  
Arterial Blood ◽  
Buccal Absorption ◽  
Elimination Half ◽  
Fentanyl Administration

Background Analgesia and sedation have been achieved noninvasively by fentanyl administration through the oral and nasal mucosa. In theory, the transmucosal bioavailability and absorption of fentanyl could be improved by converting more fentanyl to the unionized form by adjusting the surrounding pH. The authors tested this hypothesis in dogs. Methods Under general anesthesia, each of six mongrel dogs was given fentanyl on repeated occasions, first intravenously (once), then by application to the buccal mucosa (six times). Buccal fentanyl administration was accomplished by placement of a pH-buffered solution of fentanyl into a specially constructed cell, which was clamped to the dog's buccal mucosa for 60 min. Fentanyl solutions with pHs of 6.6, 7.2, and 7.7 were studied to span a tenfold difference in the unionized fraction of fentanyl. Femoral arterial blood samples were sampled frequently and analyzed for fentanyl using a radioimmunoassay. Peak plasma concentration and the time of its occurrence for each buccal study were noted from the plasma concentration verses time profile. Terminal elimination half-life, bioavailability, and permeability coefficients were calculated using standard pharmacokinetic techniques. Results The variables peak plasma concentration, bioavailability, and permeability coefficient increased three- to fivefold as the pH of the fentanyl buccal solution increased and more fentanyl molecules became unionized. There was no difference in terminal elimination half-life after intravenous fentanyl (244 +/- 68 min) or buccal fentanyl administration (pH 7.7, 205 +/- 89 min; pH 7.2, 205 +/- 65 min; pH 6.6, 196 +/- 48 min). In all buccal studies regardless of pH, time to peak plasma concentration occurred within 10 min of removal of the fentanyl solutions from the buccal mucosa. Conclusions The buccal absorption, bioavailability, and permeability of fentanyl are markedly increased as the pH of the fentanyl solution becomes more basic. Most likely, this is because of an increase in the fraction of unionized fentanyl.

scholarly journals Pharmacokinetics and skin concentrations of lincomycin after intravenous and oral administration to cats

2013 ◽  
Vol 84 (1) ◽  
Author(s):  
Gabriela A. Albarellos ◽  
Laura Montoya ◽  
Graciela A.A. Denamiel ◽  
Sabrina M. Passini ◽  
María F. Landoni
Keyword(s):  
Plasma Concentration ◽  
Oral Administration ◽  
Intravenous Administration ◽  
Half Life ◽  
Pharmacokinetic Profile ◽  
Maximum Plasma ◽  
Elimination Half Life ◽  
Concentration Time ◽  
Elimination Half ◽  
Intravenous And Oral Administration

The aim of the present study was to describe the plasma pharmacokinetic profile and skin concentrations of lincomycin after intravenous administration of a 15% solution and oral administration of 300 mg tablets at a dosing rate of 15 mg/kg to cats. Susceptibility of staphylococci (n = 31) and streptococci (n = 23) strains isolated from clinical cases was also determined. Lincomycin plasma and skin concentrations were determined by microbiological assay using Kocuria rhizophila ATCC 9341 as test microorganism. Susceptibility was established by the antimicrobial disc diffusion test. Individual lincomycin plasma concentration–time curves were analysed by a non-compartmental approach. After intravenous administration, volume of distribution, body clearance and elimination half-life were 0.97 L/kg ± 0.15 L/kg, 0.17 L/kg ± 0.06 L/h.kg and 4.20 h ± 1.12 h, respectively. After oral administration, peak plasma concentration, time of maximum plasma concentration and bioavailability were 22.52 µg/mL ± 10.97 µg/mL, 0.80 h ± 0.11 h and 81.78% ± 24.05%, respectively. Two hours after lincomycin administration, skin concentrations were 17.26 µg/mL ± 1.32 µg/mL (intravenous) and 16.58 µg/mL ± 0.90 µg/mL (oral). The corresponding skin: plasma ratios were 2.08 ± 0.47 (intravenous) and 1.84 ± 0.97 (oral). The majority of staphylococci and streptococci tested in this study were susceptible to lincosamides (87.09% and 69.56%, respectively). In conclusion, lincomycin administered orally at the assayed dose showed a good pharmacokinetic profile, with a long elimination half-life and effective skin concentration. Therefore, it could be a good first option for treating skin infections in cats.

scholarly journals Effects of delivery via pressure-adjustable pneumatic gas-powered dart gun of three antimicrobial drugs (ceftiofur crystalline free acid, tildopirosin, and tulathromycin) on drug disposition and meat quality in cattle

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11822
Author(s):  
Thomas B. Hairgrove ◽  
Virginia Fajt ◽  
Ronald Gill ◽  
Rhonda Miller ◽  
Michael Miller ◽  
...  
Keyword(s):  
Half Life ◽  
Drug Disposition ◽  
Free Acid ◽  
Plasma Concentrations ◽  
Pharmacokinetic Parameters ◽  
Carcass Quality ◽  
Antimicrobial Drugs ◽  
Elimination Half Life ◽  
Routes Of Administration ◽  
Elimination Half

Background Although Beef Quality Assurance guidelines do not recommend use of darting methods to deliver drugs, cattle in the US may be raised on farms and ranches without restraint facilities, and reports from the field suggest that dart guns are being used to deliver antimicrobial drugs. Few studies report whether this route of administration results in altered drug disposition or carcass quality. Methods Forty steers were blocked by sire and then randomly assigned to treatment with saline, ceftiofur crystalline free acid, tildipirosin, or tulathromycin delivered via dart gun. To assess drug disposition, eight ceftiofur, six tulathromycin, and six tildipirosin-treated calves were selected to measure plasma concentrations of drugs up to 10 days after drug administration. Steers were then fed a balanced ration for approximately 6.5 months and slaughtered. To evaluate carcass quality, tenderness of steaks from darted-side and non-darted sides was evaluated via Warner–Bratzler shear force testing. Due to the prohibition of extralabel routes of administration for ceftiofur in the U.S., animals treated with this drug did not enter the food supply. Results Ceftiofur disposition differed from published reports with lower mean Cmax but similar mean apparent elimination half-life. Tildipirosin disposition differed from published reports with lower Cmax and shorter apparent elimination half-life. Tulathromycin was similar to previous published reports but Cmax and apparent elimination half-life was highly variable. All steaks (from darted and non-darted sides) from cattle treated with ceftiofur and saline were more tender than from cattle treated with tulathromycin or tildipirosin (P = 0.003). There was a trend toward more tenderness in steaks from the non-darted compared to the darted side. Steaks from the darted side for one treatment, tildipirosin, were less tender than the non-darted side. Conclusions Pharmacokinetic parameters of ceftiofur crystalline free acid, tildipirosin, and tulathromycin to cattle using pressure-adjustable pneumatic gas-powered dart gun were estimated in this study. Delivery of tildipirosin and tulathromycin to cattle with dart gun may also result in detectable decreases in tenderness of harvested steaks.

Azithromycin: An Assessment of Its Pharmacokinetics and Therapeutic Potential in CAPD

2001 ◽  
Vol 21 (4) ◽  
pp. 372-377 ◽  
Author(s):  
James R. Kent ◽  
Michael K. Almond ◽  
Soraya Dhillon
Keyword(s):  
Peritoneal Dialysis ◽  
Half Life ◽  
Therapeutic Potential ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Future Research ◽  
Renal Unit ◽  
Elimination Half Life ◽  
Elimination Half ◽  
The Mean

Background Azithromycin is an azalide antibiotic with a similar antibacterial spectrum to erythromycin but with greater gram-negative activity. Azithromycin displays a favorable pharmacokinetic profile, with improved absorption and higher sustained tissue concentrations compared with erythromycin. This results in a prolonged elimination half-life, suggesting a potential for treating continuous ambulatory peritoneal dialysis (CAPD) peritonitis. Objective This study aimed to define the potential role of azithromycin in treating CAPD peritonitis. Design The pharmacokinetics and peritoneal dialysis (PD) clearance of azithromycin were studied following a single 500-mg oral dose of azithromycin. Blood and dialysate samples were taken over a 10-day period and assayed using high-pressure liquid chromatography. Setting The study took place within the Renal Unit at Southend Hospital NHS Trust, a district general hospital in the United Kingdom. Patients Eight patients with oliguric end-stage renal failure without peritonitis maintained on CAPD (3 x 2 L/day). Results Peak plasma concentrations occurred at 2 -3 hours with 0.35 - 1.35 mg/mL (mean 0.75). The mean elimination half-life was 84.55 hrs, and plasma clearance was 21.93 L/hour. This compares with values of greater than 40 hours and 40.8 L/hour reported in healthy volunteers. After 8 hours, the mean dialysate concentration was 0.07 mg/mL; PD clearance was 0.06 L/hr. Conclusion Azithromycin is not substantially removed by CAPD in the absence of peritonitis and cannot be recommended for widespread use in this setting at present. However, the successful use of azithromycin in CAPD peritonitis, due possibly to an intracellular drug transport mechanism, has been reported. Future research should address this possibility.

Sign in / Sign up

Export Citation Format

Share Document