Abstract:
:The intracellular pharmacokinetics of the different classes of antimicrobials into surrogate markers of tissue accumulation (alveolar macrophages and/or total alveolar cells collected by means of bronchoalveolar lavage or peripheral white blood cells) was reviewed. The aim of this review was to discuss the clinical implications of the intracellular pharmacokinetics of antibacterials, either from the therapeutic or toxicological perspective. The different pharmacokinetic behaviour of antimicrobials within cells is mainly related to their physicochemical properties (hydrophilicity and lipophilicity), and may have several clinical implications. Therapeutic efficacy against intracellular pathogens has been correlated mainly with the intracellular concentrations achieved by the different antimicrobial agents. This is relevant especially for macrolides, tetracyclines, fluoroquinolones and rifampicin in the treatment of bacterial infections such as Legionella pneumophila pneumonia, Mycoplasma pneumoniae pneumonia, non-gonococcal urethritis and chronic staphylococcal infections. Additionally, intracellular accumulation of antibacterials was correlated with the possibility of causing organ-specific toxicity, as in the case of aminoglycosides in regard to the risk of nephrotoxicity. Finally, it should be kept in mind that intracellular accumulation may also represent a drug reservoir in the case of lipophilic antimicrobials. This may become extremely relevant from the clinical standpoint when treating critically ill patients with sepsis with antibacterials. The pathophysiology of sepsis may explain why it is necessary to start therapy with an increased loading dose of hydrophilic antimicrobials to promptly achieve therapeutically effective concentrations.
journal_name
Clin Pharmacokinetjournal_title
Clinical pharmacokineticsauthors
Pea Fdoi
10.1007/s40262-017-0572-ysubject
Has Abstractpub_date
2018-02-01 00:00:00pages
177-189issue
2eissn
0312-5963issn
1179-1926pii
10.1007/s40262-017-0572-yjournal_volume
57pub_type
杂志文章,评审abstract::Ketoprofen, a potent nonsteroidal anti-inflammatory drug (NSAID) of the 2-arylpropionic acid class, has been used clinically for over 15 years in Europe, and has recently been introduced in the United States. Although it possesses a chiral centre, with only the S-enantiomer possessing beneficial pharmacological activi...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199019030-00004
更新日期:1990-09-01 00:00:00
abstract::A change in drug clearance with age is considered an important factor in determining the high prevalence of adverse drug reactions associated with prescribing medications for the elderly. Despite this, no general principles have been available to guide drug administration in the elderly, although a substantial body of...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/00003088-199834050-00003
更新日期:1998-05-01 00:00:00
abstract::The ability to deliver safe and effective moderate sedation is crucial to the ability to perform invasive procedures. Sedative drugs should have a quick onset of action, provide rapid and clear-headed recovery, and be easy to administer and monitor. A number of drugs have been demonstrated to provide effective sedatio...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-200645090-00001
更新日期:2006-01-01 00:00:00
abstract::Due to concern and debate in the epilepsy medical community and to the current interest of the US Food and Drug Administration (FDA) in revising approaches to the approval of generic drugs, the FDA is currently supporting ongoing bioequivalence studies of antiepileptic drugs, the EQUIGEN studies. During the design of ...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s40262-013-0103-4
更新日期:2013-12-01 00:00:00
abstract:BACKGROUND:Entecavir is an orally administered guanosine nucleoside analog with activity against hepatitis B virus (HBV) polymerase, which is approved for the treatment of chronic hepatitis B (CHB) infection in adults and children ≥2 years old (USA and EU). OBJECTIVE:To develop simplified entecavir dosing recommendati...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s40262-016-0420-5
更新日期:2016-12-01 00:00:00
abstract::Cyclosporin is a powerful immunosuppressive drug used in transplantation medicine and to treat autoimmune diseases. It is a lipophilic molecule, with its bioavailability dependent on food, bile and other interacting factors. Cyclosporin is extensively metabolised in the liver by the cytochrome P450 3A system, which is...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199324060-00004
更新日期:1993-06-01 00:00:00
abstract:OBJECTIVE:To obtain a pharmacokinetic profile of cyclosporin microemulsion formulation in patients with inflammatory bowel disease. PATIENTS AND PARTICIPANTS:58 consecutive patients (19 women and 39 men), aged 16 to 64 years (mean age 38 years), with a diagnosis of ulcerative colitis (29 patients) or Crohn's disease (...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/00003088-200140060-00006
更新日期:2001-01-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:Iron-rich transfusions and/or a compensatory increase in iron absorption ultimately result in iron loading in patients with β-thalassaemia. Hence, without iron chelation, iron accumulates relentlessly. Deferiprone has been shown to be capable of reducing the iron burden in patients with β-thala...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/11536630-000000000-00000
更新日期:2011-01-01 00:00:00
abstract:BACKGROUND:Recombinant methionyl human leptin (r-metHuLeptin) has demonstrated efficacy in improving hormonal and metabolic parameters in leptin-deficient states, and it has been suggested that leptin replacement may reverse metabolic adaptations during weight loss interventions. The pharmacokinetics of subcutaneously ...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/00003088-200847110-00006
更新日期:2008-01-01 00:00:00
abstract::Calcineurin inhibitors, the primary immunosuppressive therapy used to prevent alloreactivity of transplanted organs, have a narrow therapeutic index. Currently, treatment is individualized based on clinical assessment of the risk of rejection or toxicity guided by trough concentration monitoring. Advances in immune mo...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.1007/s40262-020-00923-w
更新日期:2020-11-01 00:00:00
abstract::Most of the currently available psychotropic drugs form 1 or more active metabolites during in vivo biotransformation in humans and/or animals. In some cases these metabolites are rapidly conjugated and excreted, but in others they attain blood and/or brain concentrations within the same range as, or even higher than,...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199018060-00002
更新日期:1990-06-01 00:00:00
abstract::Intraventricular administration of chemotherapy is one approach to overcoming the limited distribution of anticancer drugs and their active metabolites into the CNS. This form of regional chemotherapy has led to effective treatment of occult and overt meningeal leukaemia in humans. In contrast, the efficacy of this th...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-200544010-00001
更新日期:2005-01-01 00:00:00
abstract::A pharmacokinetic study of alpha 1-antitrypsin (ATT) was performed in 2 groups of homozygous PiZ-deficient patients (treated and untreated) and 1 group of healthy volunteers. The distribution of the 131I-labelled protein corresponds to a 3-compartment model. The intravenously administered protein diffused quickly to t...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/00003088-199223020-00007
更新日期:1992-08-01 00:00:00
abstract::The use of liposomal carriers and the modification of therapeutic molecules through the attachment of poly(ethylene glycol) [PEG] moieties ('pegylation') are the most common approaches for enhancing the delivery of parenteral agents. Although 'classical' liposomes (i.e. phospholipid bilayer vehicles) have been effecti...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-200140070-00005
更新日期:2001-01-01 00:00:00
abstract::Telithromycin is the first ketolide, which is a new class of antibacterial agents related to the macrolides that have structural modifications permitting dual binding to bacterial ribosomal RNA so that activity is retained against Streptococcus pneumoniae with macrolide-lincosamide-streptogramin(B) resistance. Clinica...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-200544090-00003
更新日期:2005-01-01 00:00:00
abstract::The pharmacokinetics of gentamicin were studied after total hip joint arthroplasties in 2 groups of 10 patients. The prosthesis was performed in the first group with 'Palacos R plus gentamicin' (normal viscosity), manufactured by Schering, and in the second group with 'Cerafix genta R' (low viscosity) manufactured by ...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/00003088-199019040-00005
更新日期:1990-10-01 00:00:00
abstract::The ability of a new multiple-dose non-linear regression analysis program to predict steady-state aminoglycoside peak and trough serum concentrations was evaluated. 30 patients receiving either amikacin (7), gentamicin (10) or tobramycin (13) were studied. A standard method of prediction which requires the collection ...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/00003088-198308050-00006
更新日期:1983-09-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Tesamorelin is a synthetic analogue of growth hormone-releasing factor (GRF), which increases basal and pulsatile growth hormone (GH) secretion and subsequently increases insulin-like growth factor (IGF)-1. Limited information is available about the pharmacokinetics of this compound. Consequen...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,随机对照试验
doi:10.1007/s40262-014-0202-x
更新日期:2015-03-01 00:00:00
abstract::Buspirone is an anxiolytic drug given at a dosage of 15 mg/day. The mechanism of action of the drug is not well characterised, but it may exert its effect by acting on the dopaminergic system in the central nervous system or by binding to serotonin (5-hydroxytryptamine) receptors. Following a oral dose of buspirone 20...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199936040-00003
更新日期:1999-04-01 00:00:00
abstract:OBJECTIVE:To determine the multiple dose pharmacokinetics of a new extended release (ER) capsule formulation of tolterodine, compared with the existing immediate release (IR) tablet, in healthy volunteers. DESIGN:Nonblind, randomised, 2-way crossover trial. PARTICIPANTS:19 healthy volunteers (7 females, 12 males), me...
journal_title:Clinical pharmacokinetics
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.2165/00003088-200140030-00006
更新日期:2001-01-01 00:00:00
abstract::Low-molecular-weight heparins are anticoagulants used in the treatment of thrombosis. They have effectiveness and safety profiles similar to those of unfractionated heparin but are considered an attractive alternative because of their predictable pharmacokinetic characteristics. In this article, we demonstrate the nee...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/11532960-000000000-00000
更新日期:2010-09-01 00:00:00
abstract:OBJECTIVE:The aims of this study were to (1) determine whether opportunistically collected data can be used to develop physiologically based pharmacokinetic (PBPK) models in pediatric patients; and (2) characterize age-related maturational changes in drug disposition for the renally eliminated and hepatically metaboliz...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s40262-018-00733-1
更新日期:2019-07-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:A simple approach is proposed to predict drug clearance in children when no paediatric data are available for drugs metabolised by cytochromes. METHODS:The maturation functions of cytochrome activity and binding proteins in plasma were combined with several measures of body size to describe dr...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s40262-017-0596-3
更新日期:2018-07-01 00:00:00
abstract::Fluorouracil is used clinically against various solid tumours. Both fluorouracil toxicity and pharmacokinetics vary highly within and between individuals. The reasons why doses are not individualised routinely are difficulties in defining, predicting and achieving an optimal fluorouracil exposure or dose because of a ...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-200645060-00002
更新日期:2006-01-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:Taurolidine is known to have antimicrobial activity. Furthermore, at lower concentrations, it has been found to exert a selective antineoplastic effect in vitro and in vivo. The aim of this study was to investigate the pharmacokinetics of taurolidine in vivo following repeated intravenous infus...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/00003088-200746060-00005
更新日期:2007-01-01 00:00:00
abstract::Despite contributing significantly to the burden of global disease, the translation of new treatment strategies for diseases of the central nervous system (CNS) from animals to humans remains challenging, with a high attrition rate in the development of CNS drugs. The failure of clinical trials for CNS therapies can b...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.1007/s40262-018-0632-y
更新日期:2018-09-01 00:00:00
abstract::The pharmacokinetic effect of extracorporeal elimination can be evaluated from the extracorporeal elimination rate constant, from the amount of drug removed, and from extracorporeal clearance. To compare the validity of these approaches in clinical practice, the effect of multiple plasma exchanges on the steady-state ...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/00003088-198510060-00004
更新日期:1985-11-01 00:00:00
abstract::Asthma is generally managed with bronchodilator therapy and/or anti-inflammatory drugs. Guidelines now advocate selection of drugs and pharmaceutical formulations (long-acting vs short-acting, inhaled vs systemic) on the basis of disease severity. Theophylline has a narrow therapeutic margin. Clearance is highly varia...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199426050-00006
更新日期:1994-05-01 00:00:00
abstract::For the past 300 years antimalarial dosage regimens have not been based on pharmacokinetic information. However, now that this information is available, it is appropriate to examine current recommendations for prophylaxis and treatment. In healthy subjects, the cinchona alkaloids (quinine and quinidine), primaquine an...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-198510030-00001
更新日期:1985-05-01 00:00:00
abstract::Analogues of human insulin have been developed to more closely replicate the physiology of meal-related and basal insulin secretion. Three rapid-acting analogues and two basal analogues are available for clinical use. Insulin aspart and insulin lispro have nearly identical pharmacokinetic and pharmacodynamic profiles ...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-200847090-00003
更新日期:2008-01-01 00:00:00