Pharmacokinetics of Doxycycline in Adults with Cystic Fibrosis

Beringer, Paul M.; Owens, Heather; Nguyen, Albert; Benitez, Debbie S.; Rao, Adupa P.; D’Argenio, David Z.

doi:10.1128/aac.05710-11

Cited by 51 publications

(40 citation statements)

References 22 publications

(27 reference statements)

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“…In the study of Beringer et al (6) noncompartmental pharmacokinetic analysis indicated that a less than dose-proportional relationship may be present in a small cystic fibrosis population dosed with multiple 40-mg, 100-mg, or 200-mg doses of oral doxycycline. The mean exponent values of the power model used to determine dose nonproportionality were 0.75 and 0.74 for C max and AUC inf , respectively.…”

Section: Discussionmentioning

confidence: 99%

“…Previously Beringer et al (6) performed a compartmental pharmacokinetic analysis in 20 adults with cystic fibrosis dosed with multiple 40-mg, 100-mg, or 200-mg doses of oral doxycycline (formulation unspecified) and found a two-compartment model with a lag on firstorder absorption to best describe the plasma concentration-time data. Similar results were found here, albeit the present study is a population analysis based on extensive single-and multidose oral data, and a two-transit absorption compartment model performed considerably better than a delay (lag) on simple first-order absorption.…”

Section: Discussionmentioning

confidence: 99%

“…Studies 10, 20, 30, 50, 60, and 80 were single-dose studies, and plasma samples were acquired at nominal times approximate to 0, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4,6,8,10,12,16,24,36,48,72, and 96 h after the dose on day 1 of that period. Study 40 was a single-treatment period multidose study, where participants were dosed seven times at 24-h intervals, and plasma samples were collected at nominal times of 0, 0.25, 0.…”

Section: Methodsmentioning

confidence: 99%

“…Previously, Beringer et al (6) performed a compartmental pharmacokinetic analysis in 20 adults with cystic fibrosis dosed with multiple 40-mg, 100-mg, or 200-mg doses of oral doxycycline (formulation unspecified) and found a twocompartment model with a delay (lag) on first-order absorption to best describe the plasma concentration-time data. To our knowledge, there are no population pharmacokinetic analyses in the literature exploring doxycycline concentrations following oral administration.…”

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confidence: 99%

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Population Pharmacokinetic Model of Doxycycline Plasma Concentrations Using Pooled Study Data

Hopkins

Wojciechowski

Abuhelwa

et al. 2017

Antimicrob Agents Chemother

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The literature presently lacks a population pharmacokinetic analysis of doxycycline. This study aimed to develop a population pharmacokinetic model of doxycycline plasma concentrations that could be used to assess the power of bioequivalence between Doryx delayed-release tablets and Doryx MPC. Doxycycline pharmacokinetic data were available from eight phase 1 clinical trials following single/ multiple doses of conventional-release doxycycline capsules, Doryx delayed-release tablets, and Doryx MPC under fed and fasted conditions. A population pharmacokinetic model was developed in a stepwise manner using NONMEM, version 7.3. The final covariate model was developed according to a forward inclusion (P Ͻ 0.01) and then backward deletion (P Ͻ 0.001) procedure. The final model was a twocompartment model with two-transit absorption compartments. Structural covariates in the base model included formulation effects on relative bioavailability (F), absorption lag (ALAG), and the transit absorption rate (KTR) under the fed status. An absorption delay (lag) for the fed status (FTLAG2 ϭ 0.203 h) was also included in the model as a structural covariate. The fed status was observed to decrease F by 10.5%, and the effect of female sex was a 14.4% increase in clearance. The manuscript presents the first population pharmacokinetic model of doxycycline plasma concentrations following oral doxycycline administration. The model was used to assess the power of bioequivalence between Doryx delayed-release tablets and Doryx MPC, and it could potentially be used to critically examine and optimize doxycycline dose regimens.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Population Pharmacokinetic Model of Doxycycline Plasma Concentrations Using Pooled Study Data

Hopkins

Wojciechowski

Abuhelwa

et al. 2017

Antimicrob Agents Chemother

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“…In recent times, the advancement in the study of tetracycline has developed due to their ability to inhibit matrix metalloproteinase (MMPs) in a variety of cancers such as breast, colorectal, osteosarcoma, melanoma, leukemia and prostate cancers [8]. Additionally, doxycycline has shown favorable effects in trial models of pulmonary fibrosis, emphysema, asthma and acute lung injury [9]. It also has many additional properties such as they provide anti-resorption result and prevent tissue breakdown by the inhibition of clastic cells and the inhibition of mammalian collagenases respectively.…”

Section: Introductionmentioning

confidence: 99%

Comparative Study of Three Different Brands of Doxycycline Capsules Available in Karachi

Naveed¹,

Waheed²

2014

OALib

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Doxycycline (DOX) is lipophilic and synthetic derivative of tetracycline. DOX is a bacteriostatic agent that is active against gram-positive and gram-negative aerobic and anaerobic bacteria, Mycoplasmas, Chlamydiae, Rickettsiae, and some Protozoa. It inhibits the protein synthesis by restricting the binding of RNA to 30S ribosomal subunit. It is used for inflammatory conditions; periodontitis and acute coronary syndromes, variety of cancers, pulmonary fibrosis, emphysema, asthma, acute lung injury and for prophylaxis of malaria. The aim of this study is to evaluate the pharmaceutical equivalence of the three different brands of doxycycline capsules available in Karachi, Pakistan. For this purpose three different brands of doxycycline capsules (100 mg) were randomly selected from the local market using probability tools and evaluated for quality control parameters which are weight variation, disintegration and dissolution tests specified by BP/USP (British and United state Pharmacopoeia). Weight variation values of all brands comply with USP limits. Disintegration time for all brands was within 15 minutes also complying with the USP specification. All brands exhibited more than 80% drug release within 20 minutes. The present outcomes suggest that all the three brands of doxycycline capsule available in Karachi meet the USP specification for quality control analysis.

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Single versus combination intravenous antibiotic therapy for people with cystic fibrosis

Elphick

Tan²

2014

Cochrane Database of Systematic Reviews

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Pharmacokinetics of Doxycycline in Adults with Cystic Fibrosis

Cited by 51 publications

References 22 publications

Population Pharmacokinetic Model of Doxycycline Plasma Concentrations Using Pooled Study Data

Population Pharmacokinetic Model of Doxycycline Plasma Concentrations Using Pooled Study Data

Comparative Study of Three Different Brands of Doxycycline Capsules Available in Karachi

Single versus combination intravenous antibiotic therapy for people with cystic fibrosis

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