Effect of oral antacid administration on the pharmacokinetics of intravenous doxycycline

Nguyen, Vinh; Nix, David E.; Gillikin, S; Schentag, Jerome J.

doi:10.1128/aac.33.4.434

Cited by 25 publications

(9 citation statements)

References 10 publications

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“…Fifteen antimicrobial agents were chosen, based on their recommended use for therapy or prophylaxis of meningococcal infections. PK-PD parameters, protein binding, and the variability of these measurements, were obtained from the published literature for ampicillin, azithromycin, cefotaxime, ceftriaxone, chloramphenicol, ciprofloxacin, doxycycline, levofloxacin, meropenem, minocycline, penicillin G, rifampicin, sulphafurazole, tetracycline and trimethoprim-sulphamethoxazole (Table 1) [8][9][10][11][12][13][14][15][16][17][18][19][20][21]. Data concerning penetration into the cerebrospinal fluid (CSF) were also obtained from the literature [22][23][24].…”

Section: Antimicrobial Agentsmentioning

confidence: 99%

The contribution of pharmacokinetic–pharmacodynamic modelling with Monte Carlo simulation to the development of susceptibility breakpoints for Neisseria meningitidis

Burgess

Frei

Lewis

et al. 2007

Clinical Microbiology and Infection

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This study used pharmacokinetic-pharmacodynamic (PK-PD) modelling and MICs of 15 antimicrobial agents, derived from testing a large international culture collection, to assist in the development of interpretative criteria, i.e., breakpoints, for Neisseria meningitidis. PK parameters, protein binding, percentage penetration into cerebrospinal fluid (CSF), and the variability of these values, were extracted from the published literature for the 15 agents. PK-PD parameters have not been developed specifically for N. meningitidis in animal or human studies. Thus, it was necessary to invoke PK-PD targets from other organisms that cause infections at similar sites. The PK-PD targets utilised were: time above the MIC for at least 50% of the dosing interval for all beta-lactams, chloramphenicol, sulphafurazole and trimethoprim-sulphamethoxazole; an AUC/MIC ratio of >or=25 for the tetracyclines and macrolides; and an AUC/MIC ratio of >or=125 for the fluoroquinolones. A 10 000-subject Monte Carlo simulation was designed with the usual dosing regimens of each antimicrobial agent at MIC values of 0.03-64 mg/L in both serum and CSF. The PK-PD breakpoint was defined as the MIC at which the calculated target attainment was >or=95%. Using these assumptions, the proposed PK-PD breakpoints were: azithromycin, 0.125 mg/L; doxycycline, 0.25 mg/L; cefotaxime, ciprofloxacin and levofloxacin, 0.5 mg/L; penicillin G, meropenem, rifampicin, tetracycline and minocycline, 1 mg/L; chloramphenicol and sulphafurazole, 2 mg/L; and ampicillin, ceftriaxone and trimethoprim-sulphamethoxazole, 4 mg/L. Proposed PK-PD breakpoints applicable to CSF were: penicillin and cefotaxime, 0.06 mg/L; rifampicin, 0.125 mg/L; ceftriaxone, meropenem and trimethoprim-sulphamethoxazole, 0.25 mg/L; ampicillin, 0.5 mg/L; and chloramphenicol, 1 mg/L.

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Section: Antimicrobial Agentsmentioning

confidence: 99%

The contribution of pharmacokinetic–pharmacodynamic modelling with Monte Carlo simulation to the development of susceptibility breakpoints for Neisseria meningitidis

Burgess

Frei

Lewis

et al. 2007

Clinical Microbiology and Infection

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“…Concurrent ferrous sulfate, antacids, phenobarbital, heavy alcohol intake, and undernutrition are known to accelerate the clearance of doxycycline (11,12,13,15,16,21). It is not known whether the pharmacokinetics of doxycycline are affected by same-day ferrous sulfate or malaria, and there is little information on the in vitro sensitivity of P. falciparum parasites to doxycycline (3,8,18,23).…”

mentioning

confidence: 99%

Pharmacokinetics of Oral Doxycycline during Combination Treatment of Severe Falciparum Malaria

Newton

Chaulet

Brockman

et al. 2005

Antimicrob Agents Chemother

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“…In a previous study involving doxycycline (5), a less intensive antacid regimen resulted in a 45% increase in total body clearance, from 2.24 + 0.39 to 3.25 + 0.74 liters/h. Thus, the mean additional clearance resulting from antacid treatment was 1.01 liters/h for doxycycline.…”

Section: Resultsmentioning

confidence: 87%

Effect of oral antacids on disposition of intravenous enoxacin

Nix

Lebsack

Chapelsky

et al. 1993

Antimicrob Agents Chemother

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The effect of an intensive aluminum-magnesium hydroxide antacid regimen (Maalox TC) on the disposition of intravenous enoxacin was studied in six male and six female volunteers. A single 400-mg dose of enoxacin was administered intravenously over 30 min on two occasions separated by a 1-week washout period. Thirty milliliters of Maalox TC was administered at -8, -2.5, -0.5, 1.5, 3.5, 5.5, 7.5, 9.5, 11.5, 13.5, and 15.5 h relative to the start of one enoxacin infusion. The enoxacin dose in which antacid was coadministered was randomly selected. Fourteen plasma samples were collected over 24 h, and urine was collected in two divided intervals over 48 h. Enoxacin concentrations in plasma and urine samples were determined by highperformance liquid chromatographic assays. The intensive antacid regimen did not change the total clearance (P = 0.058) or steady-state volume of distribution (P = 0.516) for enoxacin. However, the nonrenal clearance and half-life were significantly altered (P < 0.05). Antacids containing magnesium and aluminum salts result in marked reductions in concentrations in plasma and the area under the plasma concentration-versus-time curve (AUC) of enoxacin and other fluoroquinolones after concurrent oral administration (1-3). This drug interaction occurs in part because of the reduced amount of absorption of the fluoroquinolone-metal ion complexes. Other mechanisms may increase the elimination rate of fluoroquinolones. After intravenous enoxacin administration to rats, 45% of a dose of 50 mg/kg of body weight was recovered in the feces; however, biliary excretion accounted for only 2.5% of the dose (4). It is likely that either intestinal secretion or diffusion of enoxacin through the gastrointestinal mucosa is responsible. If this is the case, antacids could reduce the reabsorption of drug entering the intestinal lumen and may also promote gastrointestinal dialysis. In the study described here, we examined the effect of an intensive antacid (Maalox TC) regimen on the disposition of intravenously administered enoxacin. MATERIALS AND METHODSThe study was reviewed and approved by a licensed human research committee, and written informed consent was obtained from all volunteers. The study included 12 subjects (six males and six females). teers had a negative urine screen for drugs of abuse and had not received any medications within 2 weeks of the study.Enoxacin (400 mg) was administered as a single 30-min intravenous infusion on two occasions, 1 week apart. Thirty milliliters of aluminum-magnesium hydroxide antacid (Maalox TC; W. H. Rorer, Inc., Fort Washington, Pa.) was administered at 8, 2.5, and 0.5 h before and at 1.5, 3.5, 5.5, 7.5, 9.5, 11.5, 13.5, and 15.5 h following one of the enoxacin doses. The subjects were randomized to receive the Maalox TC regimen with either the first or second enoxacin dose in a crossover fashion. Breakfast, lunch, and dinner were of low fat content, and mealtimes relative to the enoxacin dose were standardized.At 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, a...

show abstract

Effect of oral antacid administration on the pharmacokinetics of intravenous doxycycline

Cited by 25 publications

References 10 publications

The contribution of pharmacokinetic–pharmacodynamic modelling with Monte Carlo simulation to the development of susceptibility breakpoints for Neisseria meningitidis

The contribution of pharmacokinetic–pharmacodynamic modelling with Monte Carlo simulation to the development of susceptibility breakpoints for Neisseria meningitidis

Pharmacokinetics of Oral Doxycycline during Combination Treatment of Severe Falciparum Malaria

Effect of oral antacids on disposition of intravenous enoxacin

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