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Effect of Concurrent Naproxen Administration on Pharmacokinetics of Isoniazid
Muhammad Tayyab Ansari,Bashir Ahmed Loothar,Qasim Jahangir Khan
Pakistan Journal of Biological Sciences , 2003,
Abstract: Antibacterial drugs, such as isoniazid can interact with other drugs in a wide variety of clinically significant ways. It is frequently administered with other prescription medications. The antibacterial agents may be affected by the action of another co-administered drug. Interactions involving antimicrobials often result from alterations in the hepatic metabolism or renal elimination of the drugs concurrently administered. Nonsteroidal anti-inflammatory drugs (NSAIDS) are the most widely used drugs. Drug interactions with this class of compounds are frequently reported and can be pharmacokinetics and/or pharmacodynamic in nature. Isoniazid and naproxen are co-administered in patients suffering from tuberculosis as well as osteoarthritis (mostly in developing countries). The aim of this investigation was to assess the effect of naproxen (500 mg) on the pharmacokinetics characteristics of isoniazid (300 mg) in ten healthy human volunteers in a complete cross-over design using high performance liquid chromatography (HPLC) method to analyze serum drug concentrations. Naproxen caused a highly significant (p<0.001) increase in AUC, significant (p<0.05) increase in elimination half life (t 1/2) and time for the maximum drug concentration (tmax) while significant (p<0.05) decrease in elimination rate constant (Ke). Insignificant decrease and increase was observed in absorption rate constant (Ka) and maximum drug concentration (Cmax), respectively. These results signify that naproxen enhances the concentration of isoniazid in serum therefore there is no harm to use them concurrently.
Pharmacokinetics of BMEDA after Intravenous Administration in Beagle Dogs  [PDF]
Chih-Hsien Chang,Si-Yen Liu,Te-Wei Lee
Molecules , 2014, DOI: 10.3390/molecules19010538
Abstract: The pharmacokinetics of N, N-bis(2-mercapatoethly)- N', N'-diethylenediamine (BMEDA), a molecule that can form a chelate with rhenium-188 ( 188Re) to produce the 188Re-BMEDA-liposomes, was studied. In this work, beagles received a single injection of BMEDA, at doses of 1, 2, or 5 mg/kg; the concentration of BMEDA in the beagles’ plasma was then analyzed and determined by liquid chromatography-mass spectrometry/mass spectrometry. Based on the pharmacokinetic parameters of BMEDA, we found that male and female animals shared similar patterns indicating that the pharmacokinetics of BMEDA is independent of gender differences. In addition, the pharmacokinetics of BMEDA was seen to be non-linear because the increase of mean AUC 0–t and AUC 0–∞ values tend to be greater than dose proportional while the mean Vss and CL values of BMEDA appeared to be dose dependent. The information on the pharmacokinetics of BMEDA generated from this study will serve as a basis to design appropriate pharmacology and toxicology studies for future human use.
Pharmacokinetics of Ofloxacin in Male Volunteers Following Oral Administration  [PDF]
Amjad Hameed,Tahira Iqbal,Muhammad Nawaz,Faiz Batool
Pakistan Journal of Biological Sciences , 2002,
Abstract: Ofloxacin a synthetic fluorinated analog of nalidixic acid is broad spectrum antibiotic. This study was designed to find pharmacokinetics of ofloxacin in healthy male volunteers under indigenous conditions. A total of 15 healthy male volunteers were included in this study. Ofloxacin (200 mg) was administered orally and blood samples were collected at different time intervals. The blood samples were analyzed for drug concentration by microbiological assay. The plasma concentration verses times data was used to determine pharmacokinetics parameters by one compartment model kinetic analysis. The mean (SD) values for different parameters were, absorption rate constant (Ka) 7.833 (8.683) l h -1, area under curve (AUC) 14.545 (4.304) h, mg l -1, total body clearance (CI) 14.913 (4.373) l h -1, volume of distribution (Vd) 130.76 (25.598) l, elimination half life (t1/2 ) 6.419 (1.789) h, elimination rate constant (k10 ) 0.154 (0.139) l h -1, mean residence time (MRT) 10.104 (2.384) h, absorption half life (t1/2α ) 0.212 (0.151) h, time to maximum concentration (tmax) 1.397 (0.599) h and maximum concentration (Cmax) 1.416 (0.305)micro grams ml -1. Values of parameters like Vd, AUC and Cl were comparable with foreign studies. While t1/2β , Ka were higher, and C max , tmax were lower in local population as compared with the foreign studies.
Effect of moxifloxacin administration on pharmacokinetics of tolfenamic acid in rats
Patel, Satish D.;Sadariya, Kamlesh A.;Gothi, Anil K.;Patel, Urvesh D.;Gohil, Pradhuman A.;Jain, Mukul R.;Bhavsar, Shailesh K.;Thaker, Aswin M.;
Brazilian Archives of Biology and Technology , 2011, DOI: 10.1590/S1516-89132011000400013
Abstract: pharmacokinetics of tolfenamic acid as a single drug (4 mg/kg, intramuscularly) and its co-administration with moxifloxacin (5 mg/kg, intramuscularly) in wistar rats were studied. the plasma drug concentration of tolfenamic acid was assayed by lc-ms/ms. following intramuscular administration of tolfenamic acid as single drug and in combination with moxifloxacin in male rats, the mean values of observed peak plasma drug concentration (cmax), area under plasma drug concentration-time curve (auc(0-¥) ), volume of distribution (vz), half-life (t?) and clearance (cl) were 4111.44 ± 493.15 and 3837.69 ± 351.83 ng/ml, 20280.77 ± 3501.67 and 15229.18 ± 678.80 ng.h/ml, 822.17 ± 115.38 and 1249.64 ± 139.52 ml, 2.59 ± 0.16 and 3.27 ± 0.32 hr, and 218.39 ± 25.47 and 265.18 ± 11.36 ml/hr, respectively. the peak plasma drug concentration (cmax) was significantly higher in female rats compared to male rats. the volume of distribution (vz) of the drug was significantly higher (p < 0.05) in moxifloxacin-treated male rats compared to female rats. concomitant administration of moxifloxacin may alter the disposition of tolfenamic acid in male rats.
BIOAVAILABILITY AND PHARMACOKINETICS OF NORFLOXACIN AFTER INTRAMUSCULAR ADMINISTRATION IN GOATS  [PDF]
WAJEEHA, F. H. KHAN AND I. JAVED
Pakistan Veterinary Journal , 2006,
Abstract: Bioavailability and pharmacokinetics of two commercially available preparations of norfloxacin i.e. A (imported) and B (locally prepared) were determined in six healthy female goats after single intramuscular administration @ 5 mg/kg b.wt following crossover study design. The blood samples collected at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8 and 12 hours postmedication were also analysed for drug concentration by microbiological assay. Results revealed that preparation A showed higher (p<0.05) plasma drug levels than the preparation B at 1, 3, 6 and 8 hours after medication. Among bioavailability parameters AUC ( g.h/ml) and relative bioavailability (F%) were higher for preparation A than the preparation B, while other parameters did not differ between the two preparations. Similarly, various pharmacokinetic parameters did not show any statistical difference between preparation A and B. The study revealed comparable elimination kinetics but different bioavailability of two commercial preparations of norfloxacin. It is concluded from the study that for optimal dosage regimen of drugs, the bioequivalence studies and kinetic behavior of the drugs are of paramount importance.
HIV/AIDS treatment and physicochemical quality control of medicines: evaluation of non-generic lamivudine + zidovudine tablets manufactured in Brazil
Beck, Ruy Carlos Ruver;Athayde, Margareth Linde;Cardoso, Simone Gon?alves;
Brazilian Journal of Infectious Diseases , 2007, DOI: 10.1590/S1413-86702007000600003
Abstract: in this work it was evaluated the physicochemical quality of lamivudine + zidovudine tablets, whose association belongs to the list of drugs distributed by the brazil's national program on sexually transmitted diseases and aids. four non-generic products (lamivudine + zidovudine tablets) were analyzed. they were obtained from different brazilian manufacturers, besides a reference product. the quality was evaluated by physicochemical tests described in the official codes. a validated reversed-phase high performance liquid chromatography (hplc) method was used for the assay of the active substances. all samples were in accordance to the requisites in relation to their physicochemical characteristics. dissolution studies showed similar drug percentual dissolved among all samples. the results reflect the interest of the national pharmaceutical industry to ensure the delivery of safer and cheaper drugs to the brazilian people, with particular importance in the national program on sexually transmitted diseases and aids.
Study of pharmacokinetics and tissue distribution of liposomal brucine for dermal administration  [cached]
Yang B-C,Chu Z-F,Zhu S,Wang L-J
International Journal of Nanomedicine , 2011,
Abstract: Bai-Can Yang1, Zhi-Feng Chu1, Sha Zhu1, Li-Jun Wang1, Yu-Hong Feng1, Feng-Hua Li1, Chang-Sheng Liu2, Yuan Yuan21Pharmacy Department of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Key Laboratory for Ultrafine Materials of Ministry of Education, and Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai, People’s Republic of ChinaObjective: To evaluate the pharmacokinetics and tissue distribution of liposomal brucine (LB) for dermal application.Methods: Pharmacokinetics and tissue distribution were studied by in vivo animal testing. High performance liquid chromatography (HPLC) was used to detect the concentration of brucine in rats’ skin, plasma and various tissues.Results: After dermal administration, LB was absorbed rapidly in the skin and could be detected after 0.5 hours. After 36 hours, levels were too low to be detected. In plasma, levels were also too low to be detected after 36 hours. The concentration of LB reached 50% of the maximum in all tissues except the brain, peaking after 1.5 hours but still detectable after 12 hours.Conclusion: The concentration of LB was high in skin at the application site. LB was quickly absorbed into tissues through the blood circulation and widely distributed throughout the whole body. There was no obvious toxicity and LB did not readily accumulate in tissues and organs. It showed local potency but low overall systemic toxicity.Keywords: liposomal brucine, dermal administration, pharmacokinetics, tissue distribution
Prehospital Medication Administration: A Randomised Study Comparing Intranasal and Intravenous Routes  [PDF]
Cian McDermott,Niamh C. Collins
Emergency Medicine International , 2012, DOI: 10.1155/2012/476161
Abstract: Introduction. Opioid overdose is an ever-increasing problem globally. Recent studies have demonstrated that intranasal (IN) naloxone is a safe and effective alternative to traditional routes of naloxone administration for reversal of opioid overdose. Aims. This randomised controlled trial aimed to compare the time taken to deliver intranasal medication with that of intravenous (IV) medication by advanced paramedic trainees. Methods. 18 advanced paramedic trainees administered either an IN or IV medication to a mannequin model in a classroom-based setting. The time taken for medication delivery was compared. End-user satisfaction was assessed using a 5-point questionnaire regarding ease of use and safety for both routes. Results. The mean time taken for the IN and IV group was 87.1 seconds and 178.2 seconds respectively. The difference in mean time taken was 91.1 seconds (95% confidence interval 55.2 seconds to 126.9 seconds, ). 89% of advanced paramedic trainees reported that the IN route was easier and safer to use than the IV route. Conclusion. This study demonstrates that, amongst advanced paramedic trainees, the IN route of medication administration is significantly faster, better accepted and perceived to be safer than using the IV route. Thus, IN medication administration could be considered more frequently when administering emergency medications in a pre-hospital setting. 1. Introduction The mortality associated with opioid overdose has continued to increase globally in recent years. In 2009, the number of Irish drug-related deaths attributed to opioid intoxication rose by 20% [1], while in Europe, opioids were responsible for 75% of all drug-related deaths [2]. In the United States in 2007, there were 11,499 deaths resulting from opioid overdose [3]. The main cause of death is as a result of opioid-induced respiratory depression [4]. After the initiation of basic life support measures, naloxone is an opioid antagonist that is used to reverse respiratory depression and mental state changes. It is widely marketed under the brand name Narcan. The common routes of administration of naloxone are intravenous (IV), intraosseous (IO), intramuscular (IM), and subcutaneous. Intranasal (IN) administration is an alternative route for naloxone delivery [5]. When a patient presents in opioid-induced cardiorespiratory arrest, immediate effective antagonism by naloxone reverses the opioid-induced side effects. Direct entry of naloxone into the systemic circulation is required and this is most reliably achieved with IV or IO medication administration. Vascular
Study of pharmacokinetics and tissue distribution of liposomal brucine for dermal administration
Yang B-C, Chu Z-F, Zhu S, Wang L-J, Feng Y-H, Li F-H, Liu C-S, Yuan Y
International Journal of Nanomedicine , 2011, DOI: http://dx.doi.org/10.2147/IJN.S17255
Abstract: udy of pharmacokinetics and tissue distribution of liposomal brucine for dermal administration Original Research (4106) Total Article Views Authors: Yang B-C, Chu Z-F, Zhu S, Wang L-J, Feng Y-H, Li F-H, Liu C-S, Yuan Y Published Date May 2011 Volume 2011:6 Pages 1109 - 1116 DOI: http://dx.doi.org/10.2147/IJN.S17255 Bai-Can Yang1, Zhi-Feng Chu1, Sha Zhu1, Li-Jun Wang1, Yu-Hong Feng1, Feng-Hua Li1, Chang-Sheng Liu2, Yuan Yuan2 1Pharmacy Department of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Key Laboratory for Ultrafine Materials of Ministry of Education, and Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai, People’s Republic of China Objective: To evaluate the pharmacokinetics and tissue distribution of liposomal brucine (LB) for dermal application. Methods: Pharmacokinetics and tissue distribution were studied by in vivo animal testing. High performance liquid chromatography (HPLC) was used to detect the concentration of brucine in rats’ skin, plasma and various tissues. Results: After dermal administration, LB was absorbed rapidly in the skin and could be detected after 0.5 hours. After 36 hours, levels were too low to be detected. In plasma, levels were also too low to be detected after 36 hours. The concentration of LB reached 50% of the maximum in all tissues except the brain, peaking after 1.5 hours but still detectable after 12 hours. Conclusion: The concentration of LB was high in skin at the application site. LB was quickly absorbed into tissues through the blood circulation and widely distributed throughout the whole body. There was no obvious toxicity and LB did not readily accumulate in tissues and organs. It showed local potency but low overall systemic toxicity.
The pharmacokinetics of diminazene aceturate after intramuscular administration in healthy dogs  [cached]
D.M. Miller,G.E. Swan,R.G. Lobetti,L.S. Jacobson
Journal of the South African Veterinary Association , 2012, DOI: 10.4102/jsava.v76i3.416
Abstract: The pharmacokinetics of diminazene aceturate following intramuscular (i.m.) administration at 4.2 mg/kg was evaluated in 8 healthy German Shepherd dogs. Blood samples were collected at 19 intervals over a period of 21 days. Diminazene plasma concentrations were measured using a validated HPLC method with UV detection and a sensitivity of 25 ng/m . The in vitro and in vivo binding of diminazene to blood elements was additionally determined. Diminazene pharmacokinetics showed a large inter-individual variation after i.m. administration. It had a short absorption half-life (K01-HL of 0.11 + 0.18 h), resulting in a Cmax of 1849 + 268.7 ng/m at Tmax of 0.37 h and a mean overall elimination half-life (T1/2 ) of 5.31 + 3.89 h. A terminal half-life of 27.5 + 25.0 h was measured. At 1 h after i.m. injection, 75% of the diminazene in whole blood was in the plasma fraction. The results of this study indicate that diminazene is rapidly distributed and sequestered into the liver, followed by a slower terminal phase during which diminazene is both redistributed to the peripheral tissues and/or renally excreted. It is recommended that diminazene administered i.m. at 4.2 mg/kg should not be repeated within a 21-day period.
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