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Physiological alterations to the body, such as increased adipose (fat) tissue, can affect distribution, metabolism and clearance of drugs from the body. In particular, different considerations need to be given to hydrophilic (‘water-loving’) and lipophilic (‘fat-loving’) drugs, as these have different distributions in obese and lean people. Body size may also have an effect on liver and kidney function, with obesity believed to increase clearance of drugs.
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Available data support the notion that several antimicrobial drugs that are currently given in standard doses, should be given in higher doses to patients with large body size to help attain target effects on the body. These include β-lactams, vancomycin, fluoroquinolones, macrolides, linezolid, sulphonamides, fluconazole, aminoglycosides, daptomycin, colistin, and amphotericin B, co-trimoxazole, metronidazole and aciclovir.
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However, the complex interaction between different drugs and body size means that a standard calculation would be difficult to establish. There are many factors that could be relevant, such as body mass index (BMI), total weight, adjusted weight (fraction of excess body weight added to ideal weight), lean body weight and body surface area. For different drugs, different factors may need to be considered to calculate the right dose. This is also the case for underweight people.
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Based on the class of drug and its weight-dependent body distribution and clearance, some drugs may need to be given at greater or lesser amounts than the standard adult dose. Some drugs may need their starting dose adjusted, while others may need to have their maintenance dose changed. Others may benefit from being given at the standard dose but for a shorter or longer duration.
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Such tailored doses may be beneficial for preventing antimicrobial resistance, and preventing suppression of normal ‘friendly’ bacterial flora in the body, in addition to giving maximum effectiveness and safety for the patient.
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