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.

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.

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 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 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.

scholarly journals Population Pharmacokinetics of Dihydroartemisinin and Piperaquine in Pregnant and Nonpregnant Women with Uncomplicated Malaria

2012 ◽  
Vol 56 (4) ◽  
pp. 1997-2007 ◽  
Author(s):  
Joel Tarning ◽  
Marcus J. Rijken ◽  
Rose McGready ◽  
Aung Pyae Phyo ◽  
Warunee Hanpithakpong ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Population Pharmacokinetics ◽  
Half Life ◽  
Uncomplicated Malaria ◽  
Relative Bioavailability ◽  
Total Exposure ◽  
Elimination Half Life ◽  
Elimination Half ◽  
Pharmacokinetic Properties ◽  
Disposition Model

ABSTRACTPregnant women are particularly vulnerable to malaria. The pharmacokinetic properties of antimalarial drugs are often affected by pregnancy, resulting in lower drug concentrations and a consequently higher risk of treatment failure. The objective of this study was to evaluate the population pharmacokinetic properties of piperaquine and dihydroartemisinin in pregnant and nonpregnant women with uncomplicated malaria. Twenty-four pregnant and 24 matched nonpregnant women on the Thai-Myanmar boarder were treated with a standard fixed oral 3-day treatment, and venous plasma concentrations of both drugs were measured frequently for pharmacokinetic evaluation. Population pharmacokinetics were evaluated with nonlinear mixed-effects modeling. The main pharmacokinetic finding was an unaltered total exposure to piperaquine but reduced exposure to dihydroartemisinin in pregnant compared to nonpregnant women with uncomplicated malaria. Piperaquine was best described by a three-compartment disposition model with a 45% higher elimination clearance and a 47% increase in relative bioavailability in pregnant women compared with nonpregnant women. The resulting net effect of pregnancy was an unaltered total exposure to piperaquine but a shorter terminal elimination half-life. Dihydroartemisinin was best described by a one-compartment disposition model with a 38% lower relative bioavailability in pregnant women than nonpregnant women. The resulting net effect of pregnancy was a decreased total exposure to dihydroartemisinin. The shorter terminal elimination half-life of piperaquine and lower exposure to dihydroartemisinin will shorten the posttreatment prophylactic effect and might affect cure rates. The clinical impact of these pharmacokinetic findings in pregnant women with uncomplicated malaria needs to be evaluated in larger series.

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.

Oral Chloromycetin

PEDIATRICS ◽  
1981 ◽  
Vol 68 (5) ◽  
pp. 752-753
Author(s):  
Ralph E. Kauffman
Keyword(s):  
Oral Administration ◽  
Half Life ◽  
Dosage Form ◽  
Oral Dosage ◽  
Serum Concentrations ◽  
Elimination Half Life ◽  
Oral Dosage Form ◽  
Elimination Half ◽  
Trough Serum

The recent study by Yogev et al1 nicely demonstrates that therapeutic concentrations of chloramphenicol in serum and CSF are achieved following oral administration of chloramphenicol palmitate. However, the authors' pharmacokinetic interpretation of their data is open to question. The apparent longer half-life and higher mean peak and trough serum concentrations most likely reflect greater bioavailability and prolonged absorption of the oral dosage form compared to the intravenous preparation rather than a difference in elimination half-life.

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

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%.

scholarly journals Pharmacokinetics of tulathromycin in pregnant ewes (Ovis aries) challenged with Campylobacter jejuni

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0256862
Author(s):  
Michael Yaeger ◽  
Jonathan P. Mochel ◽  
Zuowei Wu ◽  
Paul Plummer ◽  
Orhan Sahin ◽  
...  
Keyword(s):  
Campylobacter Jejuni ◽  
Half Life ◽  
Peak Plasma ◽  
Fetal Liver ◽  
Geometric Mean ◽  
Plasma Concentrations ◽  
Ovis Aries ◽  
Elimination Half Life ◽  
Elimination Half ◽  
Predetermined Time

The purpose of this study was to evaluate the pharmacokinetics of tulathromycin in the plasma and maternal and fetal tissues of pregnant ewes when administered within 24 hours of a single, IV Campylobacter jejuni (C. jejuni) challenge. Twelve, pregnant ewes between 72–92 days of gestation were challenged IV with C. jejuni IA3902 and then treated with 1.1 ml/45.36 kg of tulathromycin subcutaneously 18 hours post-challenge. Ewes were bled at predetermined time points and euthanized either at a predetermined time point or following the observation of vaginal bleeding or abortion. Following euthanasia, tissues were collected for bacterial culture, pharmacokinetics and histologic examination. The maximum (geometric) mean tulathromycin plasma concentration was estimated at 0.302 μg/mL, with a peak level observed at around 1.2 hours. The apparent systemic clearance of tulathromycin was estimated at 16.6 L/h (or 0.28 L/kg/h) with an elimination half-life estimated at approximately 22 hours. The mean tissue concentrations were highest in the uterus (2.464 μg/g) and placentome (0.484 μg/g), and were lowest in fetal liver (0.11 μg/g) and fetal lung (0.03 μg/g). Compared to previous reports, results of this study demonstrate that prior IV administration of C. jejuni appeared to substantially alter the pharmacokinetics of tulathromycin, reducing both the peak plasma concentrations and elimination half-life. However, additional controlled trials are required to confirm those observations.

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