scholarly journals Oral bioavailability and pharmacokinetics of ciprofloxacin in patients with AIDS.

1997 ◽  
Vol 41 (7) ◽  
pp. 1508-1511 ◽  
Author(s):  
R C Owens ◽  
K B Patel ◽  
M A Banevicius ◽  
R Quintiliani ◽  
C H Nightingale ◽  
...  
Keyword(s):  
Absolute Bioavailability ◽  
Pharmacokinetic Parameters ◽  
Crossover Fashion ◽  
Time Curve ◽  
Mean Values ◽  
Severe Diarrhea ◽  
Concentration Time ◽  
Infectious Gastroenteritis ◽  
Dosing Regimens ◽  
The Mean

Few reports on the effects of AIDS on the absorption of orally (p.o.) administered agents exist. To help fill this informational gap, we administered ciprofloxacin to 12 patients with AIDS by two dosing regimens (400 mg given intravenously [i.v.] and 500 mg given p.o. every 12 h) in a randomized, crossover fashion. Pharmacokinetic parameters were determined by noncompartmental methods. Mean values (+/- standard deviations [SD]) for p.o. ciprofloxacin were as follows: peak concentration of drug in serum (Cmax), 2.94 +/- 0.51 microg/ml; time to Cmax, 1.38 +/- 0.43 h; area under the concentration-time curve from 0 to 12 h (AUC(0-12)), 12.13 +/- 3.21 microg x h/ml; and half-life (t(1/2)), 3.86 +/- 0.48 h. Mean values (+/- SD) for i.v. ciprofloxacin were as follows: Cmax, 3.61 +/- 0.82 microg/ml; time to Cmax, 1.0 h; AUC(0-12), 11.92 +/- 2.92 microg x h/ml; and t(1/2), 3.98 +/- 0.94 h. The mean percent absolute bioavailability for ciprofloxacin was calculated to be 82% +/- 13%, similar to the value for healthy volunteers. We conclude that ciprofloxacin when administered p.o. to patients with AIDS is well absorbed, as evidenced by excellent bioavailability and is not affected by gastrointestinal changes in the absence of infectious gastroenteritis and severe diarrhea.

scholarly journals Safety, toleration, and pharmacokinetics of intravenous azithromycin.

1996 ◽  
Vol 40 (11) ◽  
pp. 2577-2581 ◽  
Author(s):  
D R Luke ◽  
G Foulds ◽  
S F Cohen ◽  
B Levy
Keyword(s):  
Half Life ◽  
Active Drug ◽  
Slow Release ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Time Curve ◽  
Concentration Time ◽  
Elimination Half ◽  
The Mean ◽  
Male Subjects

To date, the clinical pharmacology of large intravenous doses of azithromycin has not been described. In the present study, single 2-h intravenous infusions of 1, 2, and 4 g of azithromycin were administered to three parallel groups (in each group, six received active drug and two received placebo) of healthy male subjects. Toleration (assessed by scores of subject-administered visual analog scale tests spanning 0 [good] to 10 [poor]), safety, pharmacokinetics, and serum motilin levels were monitored for up to 240 h after the start of each intravenous infusion. Mean nausea scores of 0.0, 0.0, 1.0, and 0.5 and abdominal cramping scores of 0.0, 0.0, 0.4, and 0.4 for 12-h periods after doses of 0, 1, 2, and 4 g of azithromycin, respectively, suggested that azithromycin was well tolerated. Because of the standardized 1-mg/ml infusates, all subjects in the 4-g dosing group complained of an urgent need to urinate. There were no consistent trends in endogenous motilin levels throughout the study. The maximum concentration of azithromycin in serum (10 micrograms/ml after a 4-g dose) and the area under the concentration-time curve (82 micrograms.h/ml after a 4-g dose) were dose related. The mean pharmacokinetic parameters were an elimination half-life of 69 h, total systemic clearance of 10 ml/min/kg, and a volume of distribution at steady state of 33.3 liters/kg. The pharmacokinetic results suggest that the long half-life of azithromycin is due to extensive uptake and slow release of the drug from tissues rather than an inability to clear the drug. Single intravenous doses of up to 4 g of azithromycin in healthy subjects are generally well tolerated, and quantifiable concentrations may persist in serum for 10 days or more.

scholarly journals Pharmacokinetics of Ritonavir and Delavirdine in Human Immunodeficiency Virus-Infected Patients

2003 ◽  
Vol 47 (5) ◽  
pp. 1694-1699 ◽  
Author(s):  
Mark J. Shelton ◽  
Ross G. Hewitt ◽  
John Adams ◽  
Andrew Della-Coletta ◽  
Steven Cox ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Systemic Exposure ◽  
Pharmacokinetic Parameters ◽  
Time Curve ◽  
Minimum Concentration ◽  
Mean Values ◽  
Immunodeficiency Virus ◽  
The Mean ◽  
Full Dosage ◽  
Delavirdine Mesylate

ABSTRACT To evaluate the pharmacokinetic effect of adding delavirdine mesylate to the antiretroviral regimens of human immunodeficiency virus (HIV)-infected patients stabilized on a full dosage of ritonavir (600 mg every 12 h), 12 HIV-1-infected subjects had delavirdine mesylate (400 mg every 8 h) added to their current antiretroviral regimens for 21 days. Ritonavir pharmacokinetics were evaluated before (day 7) and after (day 28) the addition of delavirdine, and delavirdine pharmacokinetics were evaluated on day 28. The mean values (± standard deviations) for the maximum concentration in serum (C max) of ritonavir, the area under the concentration-time curve from 0 to 12 h (AUC0-12), and the minimum concentration in serum (C min) of ritonavir before the addition of delavirdine were 14.8 ± 6.7 μM, 94 ± 36 μM · h, and 3.6 ± 2.1 μM, respectively. These same parameters were increased to 24.6 ± 13.9 μM, 154 ± 83 μM · h, and 6.52 ± 4.85 μM, respectively, after the addition of delavirdine (P is <0.05 for all comparisons). Delavirdine pharmacokinetic parameters in the presence of ritonavir included a C max of 23 ± 16 μM, an AUC0-8 of 114 ± 75 μM · h, and a C min of 9.1 ± 7.5 μM. Therefore, delavirdine increases systemic exposure to ritonavir by 50 to 80% when the drugs are coadministered.

scholarly journals Induction of theophylline clearance by rifampin and rifabutin in healthy male volunteers.

1996 ◽  
Vol 40 (8) ◽  
pp. 1866-1869 ◽  
Author(s):  
J G Gillum ◽  
J M Sesler ◽  
V L Bruzzese ◽  
D S Israel ◽  
R E Polk
Keyword(s):  
Treatment Phase ◽  
Pharmacokinetic Parameters ◽  
Theophylline Clearance ◽  
Healthy Male ◽  
Time Curve ◽  
Concentration Time ◽  
Male Volunteers ◽  
Hepatic Microsomal Enzyme ◽  
The Mean ◽  
To Receive

Rifampin and rifabutin induce the metabolism of many drugs, which may result in subtherapeutic concentrations and failure of therapy. However, differences between rifabutin and rifampin in potency of induction, and the specific enzymes which are altered, are not clear. This study, involving 12 adult male volunteers, compared the effects of 14-day courses of rifampin and rifabutin on clearance of theophylline, a substrate for the hepatic microsomal enzyme CYP1A2. Subjects were given oral theophylline solution (5 mg/kg of body weight) on day 1 and then randomized to receive daily rifampin (300 mg) or rifabutin (300 mg) on days 3 to 16. Theophylline was readministered as described above on day 15. The first treatment sequence was followed by a 2-week washout period; subjects then received the alternative treatment. Theophylline concentrations were determined for 46 h after each dose, and pharmacokinetic parameters were determined. One subject developed flu-like symptoms while taking rifabutin and withdrew voluntarily. Results from the remaining 11 subjects are reported. Compared with the baseline, the mean area under the concentration-time curve (AUC) (+/- standard deviation) for theophylline declined significantly following rifampin treatment (from 140 +/- 37 to 100 +/- 24 micrograms . h/ml, P <0.001); there was no significant change following rifabutin treatment (136 +/- 48 to 128 +/- 45 micrograms.h/ml). Baseline theophylline AUCs before each treatment phase were not different. A comparison of equal doses of rifampin and rifabutin administered to healthy volunteers for 2 weeks indicates that induction of CYP1A2, as measured by theophylline clearance, is significantly less following rifabutin treatment than it is following rifampin treatment. However, the relative induction potency for other metabolic enzymes remains to be investigated.

scholarly journals Pharmacokinetics of a Fluoronaphthyridone, Trovafloxacin (CP 99,219), in Infants and Children following Administration of a Single Intravenous Dose of Alatrofloxacin

2000 ◽  
Vol 44 (5) ◽  
pp. 1195-1199 ◽  
Author(s):  
John S. Bradley ◽  
Gregory L. Kearns ◽  
Michael D. Reed ◽  
Edmund V. Capparelli ◽  
John Vincent
Keyword(s):  
Volume Of Distribution ◽  
Intravenous Dose ◽  
Pharmacokinetic Parameters ◽  
Single Intravenous Dose ◽  
Average Standard Deviation ◽  
Time Curve ◽  
Concentration Time ◽  
Age Related ◽  
The Mean ◽  
In Infants And Children

ABSTRACT The pharmacokinetics of trovafloxacin following administration of a single intravenous dose of alatrofloxacin, equivalent to 4 mg of trovafloxacin per kg of body weight, were determined in 6 infants (ages 3 to 12 months) and 14 children (ages, 2 to 12 years). There was rapid conversion of alatrofloxacin to trovafloxacin, with an average ± standard deviation (SD) peak trovafloxacin concentration determined at the end of the infusion of 4.3 ± 1.4 μg/ml. The primary pharmacokinetic parameters (average ± SD) analyzed were volume of distribution at steady state (1.6 ± 0.6 liters/kg), clearance (151 ± 82 ml/h/kg), and half-life (9.8 ± 2.9 h). The drug was well tolerated by all children. There were no age-related differences in any of the pharmacokinetic parameters studied. Less than 5% of the administered dose was excreted in the urine over 24 h. On the basis of the mean area under the concentration-time curve of 30.5 ± 10.1 μg · h/ml and the susceptibility (≤0.5 μg/ml) of common pediatric bacterial pathogens to trovafloxacin, dosing of 4 mg/kg/day once or twice daily should be appropriate.

scholarly journals Pharmacokinetics of Single-Dose Intramuscular and Subcutaneous Injections of Buprenorphine in Common Marmosets (Callithrix jacchus)

2021 ◽  
Author(s):  
Niora J Fabian ◽  
David E Moody ◽  
Olga Averin ◽  
Wenfang B Fang ◽  
Morgan Jamiel ◽  
...  
Keyword(s):  
Single Dose ◽  
Plasma Concentration ◽  
Opioid Analgesic ◽  
Callithrix Jacchus ◽  
Pharmacokinetic Parameters ◽  
Multiple Time ◽  
Common Marmosets ◽  
Concentration Time ◽  
Dosing Regimens ◽  
The Mean

Although buprenorphine is the most frequently used opioid analgesic in common marmosets (Callithrix jacchus), thereis limited information in the literature supporting current dosing regimens used for this species. The purpose of this study was to determine the pharmacokinetic profiles of single-dose buprenorphine HCl administered intramuscularly (IM) at 0.01 mg/kg in 6 adult marmosets (1.8 to 12.8 y old; 2 males, 4 females) and subcutaneously (SQ) at 0.01 mg/kg in 6 adult marmosets(2.3-4.4 y old; 3 males, 3 females) by mass spectrometry. Blood was collected at multiple time points from 0.25 to 24 h from unsedated animals following a hybrid sparse-serial sampling design. The maximal observed plasma concentration of buprenorphine (Cmax) administered IM (2.57 ± 0.95 ng/mL) was significantly higher than administered SQ (1.47 ± 0.61 ng/mL). However, the time to Cmax (Tmax) was not statistically different between routes (17.4 ± 6 min for IM and 19.8 ±7.8 min for SQ). The time of the last quantifiable concentration of buprenorphine was 5 ± 1.67 h for IM compared with 6.33 ± 1.51 h for SQ, which was not statistically different. The mean buprenorphine plasma concentration-time curves were used to propose a dosing frequency of 4 to 6 h for buprenorphine at 0.01 mg/kg IM or SQ based on a theoretical therapeutic plasma concentration threshold of 0.1 ng/mL. Based on the mean pharmacokinetic parameters and plasma-concentration time curves, both IM and SQ routes of buprenorphine at this dose provide a rapid increase in the plasma concentration of buprenorphine above the therapeutic threshold, and may be more effective for acute rather than long-lasting analgesia. Further studies are neededto examine repeated dosing regimens and the efficacy of buprenorphine in common marmosets.

scholarly journals Pharmacokinetics of Azithromycin Administered Alone and with Atovaquone in Human Immunodeficiency Virus-Infected Children

1999 ◽  
Vol 43 (6) ◽  
pp. 1516-1519 ◽  
Author(s):  
Leock Y. Ngo ◽  
Ram Yogev ◽  
Wayne M. Dankner ◽  
Walter T. Hughes ◽  
Sandra Burchett ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Steady State ◽  
Pharmacokinetic Parameters ◽  
Time Curve ◽  
Concentration Time ◽  
Significant Difference ◽  
Immunodeficiency Virus ◽  
The Mean ◽  
Clinically Significant ◽  
To Receive

ABSTRACT To evaluate if atovaquone (ATQ) interacts pharmacokinetically with azithromycin (AZ) in human immunodeficiency virus-infected children, 10 subjects (ages, 4 to 13 years) were randomized in a crossover study to receive AZ (5 mg/kg/day) alone (ALONE) or AZ (5 mg/kg/day) and ATQ (30 mg/kg/day) simultaneously (SIM) prior to receiving AZ and ATQ staggered by 12 h. Despite a lack of significant difference in the mean AZ pharmacokinetic parameters, the steady-state values of AZ’s area under the concentration-time curve from 0 to 24 h and maximum concentration in serum were consistently lower (n = 7 of 7) for the SIM regimen than they were for the ALONE regimen. A larger study will be required to determine if ATQ affects AZ pharmacokinetics and efficacy in a clinically significant manner.

scholarly journals Pharmacokinetics of Tildipirosin in Healthy and Mycoplasma gallisepticum Infected Chickens

2021 ◽  
Vol 10 (2) ◽  
pp. 119-123
Keyword(s):  
Mycoplasma Gallisepticum ◽  
Absolute Bioavailability ◽  
Pharmacokinetic Parameters ◽  
Time Curve ◽  
Group Iii ◽  
Concentration Time ◽  
Group I ◽  
Pharmacodynamic Profile ◽  
Plasma Concentration Time Curve ◽  
Insight Into

The pharmacokinetic features of tildipirosin were explored following a single dose of 4 mg/kg in healthy and Mycoplasma gallisepticum (M. gallisepticum) infected chickens. Eighteen healthy chickens (400-500g) were allocated into 3 groups (n=6); group I and II were received tildipirosin by intravenous (IV) and intramuscular (IM) routes, respectively. Group III was experimentally infected with M. gallisepticum and injected IM with tildipirosin after confirming the infection (9-10 days after inoculation of M. gallisepticum). Plasma samples were harvested at different time points until 14 days after tildipirosin injection to measure its concentrations using HPLC. After IM administration of tildipirosin in healthy chickens, the maximum concentration in plasma (Cmax), time to achieve Cmax (Tmax), area under the plasma concentration time curve from 0 to last time (AUC0-last), clearance (Cl-F-obs) and the absolute bioavailability were recorded to be 403.76ng/ml, 0.25 hr, 6.82 µg.hr/ml, 0.56L/hr/kg, and 103.50% respectively. Cmax and AUC0-last, were significantly lower in infected than healthy chickens, while Cl-F-obs was significantly higher in infected than healthy chickens. Therefore, M. gallispeticum infection produced significant changes in some of the pharmacokinetic parameters of tildipirosin in chickens. Further studies are warranted to assess pharmacokinetic/ pharmacodynamic profile of tildipirosin against M. gallisepticum in chickens and to gain deeper insight into its safety utilization in chickens.

Comparative Bioavailability and Safety of Two Intramuscular Ceftriaxone Formulations

1996 ◽  
Vol 30 (11) ◽  
pp. 1223-1226 ◽  
Author(s):  
Encarnación C Suárez ◽  
Jana R Grippi
Keyword(s):  
Plasma Concentration ◽  
Pharmacokinetic Parameters ◽  
Maximum Plasma ◽  
Double Blind ◽  
Time Curve ◽  
Mean Values ◽  
Concentration Time ◽  
Clinical Research Center ◽  
Comparative Bioavailability ◽  
Concentrated Solution

OBJECTIVE: To determine if two ceftriaxone solutions of different concentrations are bioequivalent when administered intramuscularly. DESIGN: Double-blind, single-dose, two-period, randomized crossover study. SETTING: A clinical research center. SUBJECTS: Seventeen healthy volunteers. INTERVENTION: Ceftriaxone 500 mg administered in either 2 or 1.4 mL of lidocaine 1% solution, with final ceftriaxone concentrations of 250 and 350 mg/mL, respectively. MAIN OUTCOME MEASURES: Blood samples were assayed for ceftriaxone concentrations with HPLC and pharmacokinetic parameters were calculated from the resulting plasma—concentration time profiles: maximum plasma concentration (Cmax) of ceftriaxone and areas under the concentration-time curve (AUC) from 0 to 36 h and 0 to infinity were the primary parameters considered in the determination of bioequivalence. RESULTS: The two solutions were generally well tolerated and had similar safety profiles. Administration of both solutions resulted in similar mean values for all pharmacokinetic parameters. Statistical analysis showed no significant differences between the two solutions in any pharmacokinetic parameter, indicating that the two solutions are statistically bioequivalent (p ≤ 0.05). The 90% CI for the ratio of the means for AUC0-36 (0.86 to 1.11), AUC0-∞. (0.89 to 1.14), and Cmax (0.84 to 1.12) are within the Food and Drug Administration range of bioequivalence (0.80 to 1.25). CONCLUSIONS: These results demonstrate that the more concentrated solution of ceftriaxone (350 mg/mL) is bioequivalent to the currently marketed solution of 250 mg/mL.

Absorption of Digoxin from Tablets and Capsules in Subjects with Malabsorption Syndromes

DICP ◽  
1989 ◽  
Vol 23 (10) ◽  
pp. 764-769
Author(s):  
William D. Heizer ◽  
A. Wayne Pittman ◽  
John E. Hammond ◽  
Duane D. Fitch ◽  
James A. Bustrack ◽  
...  
Keyword(s):  
Digoxin Concentration ◽  
Serum Digoxin Concentration ◽  
Pharmacokinetic Parameters ◽  
Crossover Fashion ◽  
Time Curve ◽  
Maximum Serum ◽  
Cumulative Urinary Excretion ◽  
Malabsorption Syndromes ◽  
The Mean ◽  
Male Subjects

The relative steady-state bioavailability of two oral digoxin dosage forms was studied in 17 subjects with malabsorption syndromes. Male subjects received the following treatments in randomized crossover fashion for 14 days: Three 0.125-mg digoxin tablets or three 0.1-mg digoxin capsules once daily. Female subjects received digoxin on the same schedule but at two-thirds the dose. Serum and urine samples were collected and analyzed for digoxin by radioimmunoassay, and treatments were compared by evaluating pharmacokinetic parameters. The mean area under the serum concentration versus time curve for tablets (28.1 h•nmol/L [21.9 h•ng/mL]) was smaller (p < 0.03) than that for capsules (31.1 h•nmol/L [24.3 h•ng/mL]), and the mean maximum serum digoxin concentration for tablets (2.9 nmol/L [2.3 ng/mL]) was lower (p < 0.02) than that for capsules (4.0 nmol/L [3.1 ng/mL]). There was no difference in cumulative urinary excretion of digoxin between the two treatments. In contrast to previous reports, we observed that digoxin from Lanoxin Tablets appears to be well absorbed in subjects with malabsorption. Nevertheless, these subjects absorbed digoxin from capsules better than from tablets, with the greatest differences occurring in subjects without a colon and in those subjects with the lowest serum carotene concentrations.

scholarly journals Voriconazole Pharmacokinetics and Safety in Immunocompromised Children Compared to Adult Patients

2010 ◽  
Vol 54 (8) ◽  
pp. 3225-3232 ◽  
Author(s):  
Claudia Michael ◽  
Uta Bierbach ◽  
Katrin Frenzel ◽  
Thoralf Lange ◽  
Nadezda Basara ◽  
...  
Keyword(s):  
Pediatric Patients ◽  
Fungal Infections ◽  
Adult Patients ◽  
European Medicines Agency ◽  
Pharmacokinetic Parameters ◽  
Time Curve ◽  
Entire Study ◽  
Interindividual Variations ◽  
Concentration Time ◽  
Days Of Therapy

ABSTRACT The aim of this study was to investigate the pharmacokinetics and safety of voriconazole after intravenous (i.v.) administration in immunocompromised children (2 to 11 years old) and adults (20 to 60 years old) who required treatment for the prevention or therapy of systemic fungal infections. Nine pediatric patients were treated with a dose of 7 mg/kg i.v. every 12 h for a period of 10 days. Three children and 12 adults received two loading doses of 6 mg/kg i.v. every 12 h, followed by a maintenance dose of 5 mg/kg (children) or 4 mg/kg (adults) twice a day during the entire study period. Trough voriconazole levels in blood over 10 days of therapy and regular voriconazole levels in blood for up to 12 h postdose on day 3 were examined. Wide intra- and interindividual variations in plasma voriconazole levels were noted in each dose group and were most pronounced in the children receiving the 7-mg/kg dose. Five (56%) of them frequently had trough voriconazole levels in plasma below 1 μg/ml or above 6 μg/ml. The recommended dose of 7 mg/kg i.v. in children provides exposure (area under the concentration-time curve) comparable to that observed in adults receiving 4 mg/kg i.v. The children had significantly higher C max values; other pharmacokinetic parameters were not significantly different from those of adults. Voriconazole exhibits nonlinear pharmacokinetics in the majority of children. Voriconazole therapy was safe and well tolerated in pediatric and adult patients. The European Medicines Agency-approved i.v. dose of 7 mg/kg can be recommended for children aged 2 to <12 years.

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