title: Fractal Geometry-Based Decrease in Trimethoprim-Sulfamethoxazole Concentrations in Overweight and Obese People.
abstract: Trimethoprim-sulfamethoxazole (TMP-SMX) is one of the most widely drugs on earth. The World Health Organization recommends it as an essential basic drug for all healthcare systems. Dosing is inconsistently based on weight, assuming linear relationships. Given that obesity is now a global "pandemic" it is vital that we evaluate the effect of obesity on trimethoprim-sulfamethoxazole concentrations. We conducted a prospective clinical experiment based on optimized design strategies and artificial intelligence algorithms and found that weight and body mass index (BMI) had a profound effect on drug clearance and volume of distribution, and followed nonlinear fractal geometry-based relationships. The findings were confirmed by demonstrating decreased TMP-SMX peak and area under the concentration-time curves in overweight patients based on standard regression statistics. The nonlinear relationships can now be used to identify new TMP-SMX doses in overweight and obese patients for each of the infections caused by the >60 pathogens for which the drug is indicated.
authors.affiliation: Department of Pharmacy Practice, Texas Tech University Health Sciences Center, School of Pharmacy, Austin, Texas, USA.
authors.forename: R G
authors.initials: RG
authors.lastname: Hall
authors.affiliation: Center for Infectious Diseases Research and Experimental Therapeutics, Baylor Research Institute, Baylor University Medical Center, Dallas, Texas, USA.
authors.forename: J G
authors.initials: JG
authors.lastname: Pasipanodya
authors.affiliation: Department of Pharmacy Practice, Texas Tech University Health Sciences Center, School of Pharmacy, Austin, Texas, USA.
authors.forename: C
authors.initials: C
authors.lastname: Meek
authors.affiliation: Department of Pharmacy Practice, Texas Tech University Health Sciences Center, School of Pharmacy, Austin, Texas, USA.
authors.forename: R D
authors.initials: RD
authors.lastname: Leff
authors.affiliation: Department of Medicine, UT Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: M
authors.initials: M
authors.lastname: Swancutt
authors.affiliation: Center for Infectious Diseases Research and Experimental Therapeutics, Baylor Research Institute, Baylor University Medical Center, Dallas, Texas, USA.|Department of Medicine, University of Cape Town, Observatory, Cape Town, South Africa.
authors.forename: T
authors.initials: T
authors.lastname: Gumbo
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001185:Artificial Intelligence; D001835:Body Weight; D054796:Drug Dosage Calculations; D005260:Female; D017709:Fractals; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009765:Obesity / Q000150:complications*; D050177:Overweight / Q000150:complications*; D011446:Prospective Studies; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000008:administration & dosage / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D015662:Trimethoprim, Sulfamethoxazole Drug Combination