Once bitten, twice shy: concern about gaining weight after smoking cessation and its association with seeking treatment.

BACKGROUND: Concern about weight gain after quitting smoking is often cited as a barrier to smokers making a quit attempt or seeking treatment. AIM: To identify whether smokers who are non-treatment seekers (NTS) are more concerned about weight gain and have lower confidence to maintain weight after quitting smoking as compared with treatment-seeking smokers (TS). METHODS: Participants were smokers recruited from Penn State Hershey Medical Center and family practice outpatient clinics. A total of 102 NTS and 186 TS, who participated in a smoking cessation trial, completed a survey regarding tobacco use, weight concern and diet. Stepwise logistic regression was used to identify variables associated with treatment seeking, overall and stratified by those who gained and did not gain weight on a previous quit attempt. RESULTS: Fifty three per cent of the overall sample (47.1% NTS vs. 56.5% TS, p = 0.127) had gained weight on a prior quit attempt. Among smokers who had gained weight, higher weight gain concern (WGC) and lower confidence in ability to maintain weight were significantly associated with being a NTS after adjusting for other factors. CONCLUSION: Among smokers who gained weight on a previous quit attempt, NTS had greater concern about gaining weight and less confidence in their ability to maintain their weight after quitting than treatment seekers. Clinicians can identify smokers for whom WGC may be a barrier to seeking treatment by asking if they gained weight on a previous quit attempt. These smokers should be assured that this issue will be addressed in treatment.

Lack of effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of amlodipine.

AIMS: To determine whether repeated once daily administration of grapefruit juice altered the pharmacokinetics or pharmacodynamics of the calcium antagonist amlodipine. METHOD: S The effects of grapefruit juice on the pharmacokinetics and pharmacodynamics of oral and intravenous amlodipine were assessed in 20 healthy men in a placebo-controlled, open, randomized, four-way crossover study using single doses of amlodipine 10 mg. For 9 days beginning with the day of administration of amlodipine, grapefruit juice (or water control) was given once daily, and blood samples, blood pressure and heart rate measures were obtained. Plasma concentrations of amlodipine and its enantiomers were determined in separate assays by GC-ECD. RESULTS: Oral amlodipine had high systemic availability (grapefruit juice: 88%; water: 81%). Pharmacokinetic parameters of racemic amlodipine (AUC, Cmax, tmax, and kel) were not markedly changed with grapefruit juice coadministration. Total plasma clearance and volume of distribution, calculated after intravenous amlodipine, were essentially unchanged by grapefruit juice (CL 6.65 ml min-1 kg-1, juice vs 6.93 ml min-1 kg-1, water; Vdss 22.7 l kg-1, juice vs 21.0 l kg-1, water). Grapefruit juice coadministration did not greatly alter the stereoselectivity in amlodipine oral or intravenous kinetics. The sum of S(-) and R(+) enantiomer concentrations correlated well with total racemic amlodipine concentration (r2 = 0. 957; P = 0.0001). Coadministration of grapefruit juice with either route of amlodipine administration did not significantly alter blood pressure changes vs control. CONCLUSIONS: Grapefruit juice has no appreciable effect on amlodipine pharmacodynamics or pharmacokinetics, including its stereoselective kinetics. Bioavailability enhancement by grapefruit juice, noted with other dihydropyridine calcium antagonists, does not occur with amlodipine. Once daily grapefruit juice administration with usual oral doses of amlodipine is unlikely to alter the profile of response in clinical practice.

A study of the pharmacokinetics of azithromycin and nelfinavir when coadministered in healthy volunteers.

A two-way, open-label, crossover study in 12 subjects was undertaken to study the potential for azithromycin to alter the pharmacokinetics of nelfinavir and/or its active metabolite, M8. A secondary objective was to characterize any potential interaction that nelfinavir may have with azithromycin. During one dosing arm, subjects received a single 1200 mg oral dose of azithromycin. During the other, subjects received 11 days of nelfinavir 750 mg q8h with a single 1200 mg oral dose of azithromycin given concurrently with the Day 9 morning nelfinavir dose. Serum samples were collected after each azithromycin dose for 168 hours and after the Day 8 and 9 morning nelfinavir doses for 8 hours to characterize azithromycin, nelfinavir, and M8 pharmacokinetic parameters during both control and test periods. Both dosing regimens were well tolerated, with only mild to moderate GI side effects being the most frequently reported. Azithromycin was found to cause a statistically, though not clinically, significant decrease in nelfinavir and M8 exposures. In contrast, nelfinavir caused azithromycin Cmax and exposure (AUC) values to increase by > 100%. Inhibition of p-glycoprotein by nelfinavir may be responsible for this significant interaction. This increase in azithromycin exposure has the potential to increase clinical antibacterial efficacy without significantly increasing gastrointestinal side effects, though the impact on other systemic sites needs to be studied.

Pharmacokinetic study of azithromycin with fluconazole and cotrimoxazole (trimethoprim-sulfamethoxazole) in healthy volunteers.

BACKGROUND: Azithromycin, fluconazole and cotrimoxazole (trimethoprim-sulfamethoxazole; TMP/SMX) are all agents that are utilised for the treatment and/or prophylaxis of opportunistic infections in patients with AIDS. OBJECTIVE: To characterise the potential for an interaction when azithromycin is coadministered with cotrimoxazole or with fluconazole. DESIGN: Two separate nonblind randomised studies were conducted in healthy volunteers. During the fluconazole study the potential for fluconazole to adversely affect the pharmacokinetics of azithromycin was also studied. PARTICIPANTS: 24 (cotrimoxazole) and 18 (fluconazole) healthy male and female volunteers. RESULTS: The results of both studies indicated that neither the peak concentrations of nor the exposures (area under the concentration-time curve) to the test drugs were changed when azithromycin was coadministered. In addition, fluconazole did not significantly alter the pharmacokinetic parameters of azithromycin. CONCLUSIONS: Azithromycin does not alter the bioavailability of either cotrimoxazole or fluconazole.

DNA-binding affinities of MyoD and E47 homo- and hetero-dimers by capillary electrophoresis mobility shift assay.

A simple capillary electrophoresis mobility shift assay (CEMSA), with no gel and uncoated capillaries, for the accurate determination of protein-DNA affinities free in solution was applied to constructs of the MyoD/E47 DNA-binding proteins. The determined affinities are compared to those obtained by EMSA. MyoD-E47 covalent heterodimer binds DNA more tightly (Kd=1.8 nM) than MyoD (Kd=14.2 nM) or E47 (Kd= 11.5 nM) covalent homodimers. The effect of non-specific DNA on binding affinities was more important than salt concentration in the MyoD/E47 series. Application of this method to the MyoD/E47 system demonstrates the generality of our CEMSA.

The effect of azithromycin on the pharmacokinetics of indinavir.

This study was performed to examine the effect of the coadministration of azithromycin on the pharmacokinetics of the protease inhibitor indinavir (Crixivan). In an open-label, parallel-design study, 32 healthy male and female volunteers were given indinavir (800 mg tid) for 5 days. One hour prior to the first dose of indinavir on day 5, 18 subjects received 1200 mg azithromycin (Zithromax), and 14 subjects received matching placebo. Serial samples of plasma were obtained for 8 hours following the morning dose of indinavir on days 4 and 5 and assayed for indinavir by HPLC/UV. Twenty-seven subjects completed the study. Following coadministration of azithromycin with indinavir, there was no significant change between day 5 and day 4 in AUC (20.7 mg.hr/ml and 23.1 mg.hr/ml; 90% CI on the ratio 81%-100%) or Cmax (9.88 mg/ml and 10.3 mg/ml; 90% CI 86%-108%). The day 5 to day 4 difference in indinavir concentrations following coadministration with azithromycin was not significantly different from the day 5 to day 4 difference with placebo (AUC p = 0.68; Cmax p = 0.074). Therefore, azithromycin does not significantly alter the kinetics of indinavir.

Pharmacokinetics in serum and leukocyte exposures of oral azithromycin, 1,500 milligrams, given over a 3- or 5-day period in healthy subjects.

The pharmacokinetics in serum and leukocyte (WBC) exposures of 1,500 mg of oral azithromycin administered as 3-day (500 mg/day, days 1 to 3) and 5-day (500 mg on day 1 and 250 mg/day on days 2 to 5) regimens were compared in 12 healthy volunteers. Serum, polymorphonuclear leukocytes, and mononuclear leukocytes were collected over a 12-day period from the start of each regimen. Results of the study indicate that the exposures of serum and both types of WBCs were similar with both regimens. Drug concentrations in day 12 WBCs were well above the MICs for all relevant community-acquired respiratory tract pathogens. Terminal half-lives in serum obtained by both regimens were essentially equal at 66 h and consistent with past reports. These results indicate that the standard 1,500-mg dose of oral azithromycin can be administered over either 5 or 3 days.

Ocular levels of azithromycin.

OBJECTIVE: To assess azithromycin levels in human serum, aqueous humor, tear fluid, and conjunctival tissue specimens after administration of a single 1-g oral dose of azithromycin. METHODS: Sixty patients undergoing cataract surgery were included in this analysis. Serum, aqueous, and tear specimens were collected 3, 6, and 12 hours and 1, 2, 3, and 4 days after azithromycin administration. Conjunctival tissue biopsy specimens were collected 1, 2, 3, 4, 6, 8, 10, 12, and 14 days after azithromycin administration. All specimens were subjected to analysis by high-performance liquid chromatography-mass spectrometry. RESULTS: Azithromycin concentration ranges during the specified sampling times were as follows: serum, 21 to 974 ng/mL; tear, 82 to 2892 ng/mL; aqueous, 10 to 69 ng/mL; and conjunctival, 0.7 to 32 micrograms/g. Levels above the 90% minimal inhibitory concentration (MIC90) for Chlamydia trachomatis were detected after 4 days in all tear samples and after 14 days in all conjunctival tissue specimens following oral azithromycin administration. CONCLUSION: We demonstrated prolonged high levels of azithromycin in drug-targeted ocular tissue. Prolonged high concentrations of azithromycin in conjunctival tissue make this drug suitable for treatment of conjunctivitis caused by chlamydiae and other susceptible organisms.

Comparison of azithromycin and clarithromycin in their interactions with rifabutin in healthy volunteers.

A 14-day, randomized, open, phase I clinical trial was designed to examine possible pharmacokinetic interactions between rifabutin and two other antibiotics, azithromycin and clarithromycin, used in the treatment of Mycobacterium avium complex infections. Thirty healthy male and female volunteers were divided into five groups of six participants each: 18 received 300 mg/day of rifabutin, 12 in combination with therapeutic doses of either azithromycin or clarithromycin; the remaining 12 received azithromycin or clarithromycin alone. On day 10 the study was terminated because of adverse events, including severe neutropenia. Fourteen participants who received rifabutin developed neutropenia, including all 12 participants who received azithromycin or clarithromycin concomitantly. Analyses of serum revealed no apparent pharmacokinetic interaction between azithromycin and rifabutin. However, the mean concentrations of rifabutin and 25-O-desacetyl-rifabutin (an active metabolite) in participants who received clarithromycin and rifabutin concomitantly were more than 400% and 3,700%, respectively, of concentrations in those who received rifabutin alone. Physicians should be aware that recommended prophylactic doses of rifabutin may be associated with severe neutropenia within 2 weeks after initiation of therapy, and all patients receiving rifabutin, especially with clarithromycin, should be monitored carefully for neutropenia.

A capillary electrophoresis mobility shift assay for protein-DNA binding affinities free in solution.

Quantitative determination of dissociation constants for DNA-protein complexes will help clarify the molecular mechanisms of transcription, replication and DNA repair. A practical capillary electrophoresis mobility shift assay (CEMSA) for protein-DNA affinities free in solution is presented. The method is fast and simple, precise and general. The speed (<2 min separations) and simplicity derive from the use of an uncoated capillary with no gel matrix. The dissociation constant for GCNK58, a DNA-binding-region construct of the yeast transcription factor GCN4, binding to the AP1 DNA site was measured ( K d = 35 +/- 4 nM) to demonstrate the utility of the method.

Pharmacokinetics of azithromycin after single- and multiple-doses in children.

STUDY OBJECTIVE: To characterize the disposition and tolerance of azithromycin after single and multiple oral doses of 12 mg/kg in children with and without cancer. DESIGN: Open-label, nonrandomized pharmacokinetic study. SETTING: Two pediatric hospitals. PATIENTS: Twelve children with cancer admitted to the inpatient unit for empiric antibiotic treatment of febrile neutropenia, and 16 hospitalized patients receiving antibiotic therapy INTERVENTIONS: Patients received azithromycin suspension either as a single dose or daily dose every morning for 5 consecutive days. Serial blood samples were collected up to 120 hours after a single dose or during and after multiple doses to characterize the pharmacokinetic parameters estimated for a two-compartment absorption model. MEASUREMENTS AND MAIN RESULTS: All 28 patients were evaluable for safety. Azithromycin was well tolerated except in one patient with cancer who experienced abdominal cramps and withdrew from the study. Pharmacokinetic results were not determined in five patients because of insufficient concentration-time data. The mean +/- SD estimates of oral clearance, terminal half-life, maximum concentration in serum (Cmax), and time to achieve Cmax in the 23 evaluable patients were 4.83 +/- 3.59 L/hour/kg, 54.5 +/- 36.4 hours, 318.2 +/- 174.5 microg/L, and 2.4 +/- 1.1 hours, respectively. These estimates did not differ between single-dose (14 patients) and multiple-dose (9 patients) groups. Pharmacokinetic parameters were not different between the 11 children with cancer and the 12 without cancer. CONCLUSION: Azithromycin 12 mg/kg results in proportionately higher serum concentrations than previously published results for lower doses (5 mg/kg). Variability in concentration profiles among patients is substantial, and age or other yet unidentified clinical factors may explain some of the differences observed.

Toleration of intravenous azithromycin.

OBJECTIVE: To study the toleration of various infusate concentrations of single intravenous doses of azithromycin. DESIGN: Randomized, double-blind, two-treatment, two-period, crossover. SETTING: Clinical pharmacology unit. PARTICIPANTS: Twenty-four healthy men aged 19-41 years. STUDY DESIGN: All subjects were initially randomized to receive single 1-hour intravenous infusions of azithromycin 1 g at infusate concentrations of 1, 2, or 5 mg/mL (n = 6 each) compared with placebo (n = 6). Subjects who were randomized to receive 1 mg/mL concentrations were subsequently administered 5 mg/mL concentrations at least 2 weeks later, those given 2 mg/mL were crossed over to 4 mg/mL, and those in the 5-mg/mL group were crossed over to 1 mg/mL concentrations. MAIN OUTCOME MEASURES: Subjects recorded intravenous infusion toleration using visual analog scales ranging from 0 (no signs or symptoms) to 10 (poor toleration) for erythema, pain, swelling, and tenderness. Vascular Doppler recordings were obtained during and after infusion cephalad to the infusion site. RESULTS: Infusion site reactions increased in incidence and severity with infusion concentrations of 4 and 5 mg/mL; the most frequent reactions were tenderness and erythema. There were no apparent trends in Doppler readings. CONCLUSIONS: Single doses of azithromycin 1 g at infusate concentrations up to 2 mg/mL were well tolerated when administered over 1 hour to healthy men.

Disposition of oral azithromycin in humans.

BACKGROUND: The oral bioavailability of azithromycin is approximately 37% in healthy subjects; little is known about the disposition of the remaining 63% of the dose. This study attempted to describe the fate of azithromycin before absorption. METHODS: Twelve subjects with ileostomies in place for > 1 month were studied in this open-label, randomized, three-center, two-period, two-treatment crossover study. Subjects randomly received single 500 mg intravenous infusion (over 1 hour) or two 250 mg oral capsules after a fast for > 12 hours. Blood and ileostomy samples were collected serially after each administration and analyzed for azithromycin and two metabolites (descladinose and 9a-N-desmethyl metabolites) by HPLC with electrochemical detection. RESULTS: Mean +/- SD peak concentration values after oral and intravenous administration were 0.21 +/- 0.08 and 3.40 +/- 1.12 microgram/ml. Mean values for area under the serum concentration versus time curve were 1.27 +/- 0.65 and 7.14 +/- 1.34 micrograms x hr/ml, respectively. The absolute bioavailability of 16.2% was approximately one-half the value observed previously in healthy subjects. Recovery in ileostomy fluid (percent of dose in 24 hours) or azithromycin, descladinose, and 9a-N-desmethyl metabolites were 13%, 0.5%, and 1% (total, 15%) after intravenous dosing and 47%, 13%, and 2% (total, 62%) after oral dosing. Total and ileal clearances were 776 +/- 126 and 158 +/- 63 ml/min after intravenous dosing. CONCLUSION: Because more descladinose metabolite was detected after oral dosing, acid degradation of azithromycin before absorption contributed to some loss in oral bioavailability. Further, ileal clearance (biliary plus intestinal excretion clearance) in this population represented 21% of total clearance. Taken together, these data suggest that the cause of low oral bioavailability of azithromycin is the result of incomplete absorption rather than acid degradation or extensive first-pass metabolism.

Safety, toleration, and pharmacokinetics of intravenous azithromycin.

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.

The absence of an effect of food on the bioavailability of azithromycin administered as tablets, sachet or suspension.

Present product labelling indicates that azithromycin capsules should not be taken with food. However, three recent studies demonstrated that food does not significantly decrease the bioavilabilities of three new formulations of azithromycin (250 mg tablets, 1000 mg sachet, 500 mg paediatric suspension). With a 500 mg dosage, the mean relative bioavailability of azithromycin following ingestion of a standard high-fat breakfast was 96% when administered as two 250 mg tablets and 113% when administered as a suspension. The mean relative bioavailability of a 1000 mg sachet was 112%. The absolute bioavailability of the sachet formulation, relative to a 1 h iv infusion of 1000 mg, was 44%. Thus, azithromycin tablets, suspension and sachet may be given without regard to meals, further enhancing the convenience of once-daily, short-duration dosing regimens.

Pharmacokinetics of trovafloxacin (CP-99,219), a new quinolone, in rats, dogs, and monkeys.

The pharmacokinetics of trovafloxacin [CP-99,219; 7-(3-azabicyclo[3.1.0]hexyl)-naphthyridone] were studied in rats, dogs, and monkeys following oral and intravenous administration. After intravenous dosing, the systemic clearances of trovafloxacin in rats, dogs, and monkeys were 12.5, 11.1, and 7.2 ml/min/kg of body weight, respectively, and the respective volumes of distribution were 0.9, 1.7, and 4.3 liters/kg, with corresponding elimination half-lives of 0.7, 1.8, and 7.0 h. After the administration of oral doses of 50, 20, and 20 mg/kg to rats, dogs, and monkeys serum trovafloxacin concentrations reached a maximum at 0.6, 2.3, and 2.3 h, respectively, with respective maximum concentrations of trovafloxacin in serum of 11.5, 3.5, and 5.2 micrograms/ml; the corresponding elimination half-lives were 2.2, 2.5, and 7.5 h. The oral bioavailability of trovafloxacin was 68, 58, and 85% in rats, dogs, and monkeys, respectively. The binding of trovafloxacin to serum proteins was concentration independent, averaging 92, 75, and 66% for rats, dogs, and monkeys, respectively. Trovafloxacin penetrated well into tissues in dogs. The urinary recoveries of unchanged drug were less than 5% in dogs and monkeys, with or without incubation with alkali or Glusulase (beta-glucuronidase and sulfatase). In rats, 99.8% of the orally administered radioactivity was recovered in feces, while 20.6, 3.4, and 67.1% of the radioactive dose in bile duct-cannulated rats were recovered in feces, urine, and bile, respectively. These results suggest that the elimination of trovafloxacin from rats, and possibly from dogs and monkeys, is primarily through biliary excretion.

Determination of trovafloxacin, a new quinolone antibiotic, in biological samples by reversed-phase high-performance liquid chromatography.

A simple, accurate and precise high-performance liquid chromatographic method was developed and validated for the determination of trovafloxacin, a new quinolone antibiotic, in serum and urine. Following solid-phase extraction, chromatographic separation was accomplished using a C18 column with a mobile phase consisting of 0.04 M H3PO4-acetonitrile-tetrabutylammonium hydroxide-0.005 M dibutyl amine phosphate (D-4) reagent (83:16.85:0.05:0.1, v/v), pH 3. Trovafloxacin and the internal standard (a methyl derivative of trovafloxacin) were detected by ultraviolet absorbance at 275 nm. The lower limit of quantification for trovafloxacin was 0.1 microgram/ml and the calibration curves were linear over a concentration range of 0.1 to 20.0 micrograms/ml (r2 = 0.9997). The average recoveries were greater than 70% for both trovafloxacin and internal standard. The intra-day and inter-day coefficients of variation were generally less than 5% in urine and serum over the concentration range of 0.1 to 20.0 micrograms/ml. Human serum samples could be stored for up to 12 months at -20 degrees C and urine samples could be stored up to 18 months at -80 degrees C.

Pharmacokinetics and safety of trovafloxacin (CP-99,219), a new quinolone antibiotic, following administration of single oral doses to healthy male volunteers.

Trovafloxacin (CP-99,219) is a new fluoroquinolone antibacterial agent with a broad spectrum of activity against Gram-positive and Gram-negative bacteria. The pharmacokinetics and safety of trovafloxacin were characterised in healthy male volunteers after administration of single oral doses of 30, 100, 300, 600 and 1000 mg. trovafloxacin was rapidly absorbed and serum concentrations reached a maximum approximately 1 h after dosing. The corresponding mean Cmax values (mean +/- SD) were 0.3 +/- 0.0, 1.5 +/- 0.5, 4.4 +/- 1.1, 6.6 +/- 1.4 and 10.1 +/- 0.5 mg/L. Terminal-phase half-life was independent of dose, with an overall mean of 9.9 +/- 2.5 h. Generally, Cmax and AUC0-infinity increased linearly with dose. Less than 10% of the administered dose was recovered unchanged in urine. Over the dosing range, trovafloxacin renal clearance was fairly constant, averaging 0.67 +/- 0.36 L/h. Trovafloxacin binding to serum proteins was moderate (70%). Trovafloxacin was well tolerated at doses of 300 mg or below. There were no significant changes in the clinical chemistry or haematology parameters evaluated over the entire dosing range.

Pharmacokinetics of azithromycin in pediatric patients with acute otitis media.

The objective of our study was to characterize the pharmacokinetics of azithromycin after the oral administration of multiple doses in suspension to children with acute otitis media. Thirteen children (ranging in age from 7.5 months to 5 years) received a single oral dose of 10 mg of azithromycin per kg of body weight on day 1 followed by single daily doses of 5 mg/kg on days 2 to 5. Each child fasted overnight before receiving the final dose on day 5. Multiple blood samples were collected after the last dose. Concentrations of azithromycin in serum were measured by a specific high-performance liquid chromatography-mass spectrometry method. The means and standard deviations for the maximum concentration of azithromycin in serum, the time to maximum concentration of azithromycin in serum, the area under the concentration-time curve (from 0 to 24 h), and the elimination half-life were 224 +/- 120 ng/ml, 1.8 +/- 0.4 h, 1,841 +/- 651 ng.h/ml, and 31.6 +/- 6.6 h, respectively. Concentrations in serum (means +/- standard deviations) at 0 h (predose) and at 24, 48, and 72 h after the final dose were 51 +/- 26, 47 +/- 21, 27 +/- 17, and 17 +/- 13 ng/ml, respectively. Thus, the once-daily administration of azithromycin resulted in sustained systemic exposure to the drug. The drug dosage regimen used in this study should lead to tissue drug concentrations exceeding the MICs for common pathogens.