Pharmacokinetics Made Easy Download Pdf
Harbin Pelletier
What is meant by non-linear pharmacokinetics?
When the dose of a drug is increased, we expect that the concentration at steady state will increase proportionately, i.e. if the dose rate is increased or decreased say two-fold, the plasma drug concentration will also increase or decrease two-fold. However, for some drugs, the plasma drug concentration changes either more or less than would be expected from a change in dose rate. This is known as non-linear pharmacokinetic behaviour and can cause problems when adjusting doses.
Renal excretion
In Article 7 (`Clearance of drugs by the kidneys' Aust Prescr 1992;15:16-9), it was shown that renal drug clearance is the sum of filtration clearance plus secretion clearance minus reabsorption. Clearance by glomerular filtration is a passive process which is not saturable, but secretion involves saturable drug binding to a carrier. Even when secretion is saturated, filtration continues to increase linearly with plasma drug concentration. The extent to which saturation of renal secretion results in non-linear pharmacokinetics depends on the relative importance of secretion and filtration in the drug's elimination. Because of the baseline of filtration clearance, saturation of renal secretion does not usually cause clinically important problems.
If the dosage regimen must be altered for any reason at a later stage of treatment, for example, in patients with renal failure, measuring plasma concentrations again may be helpful. Undertreatment of an established condition may be concluded if a poor clinical response is observed. However, when the drug is being used as prophylaxis, it is impossible to monitor a response. Thus, the physician can select a dosage that will produce a certain target plasma concentration. This dictum applies particularly to lithium in preventing manic-depressive attacks, to phenytoin in preventing fits after neurosurgery or trauma, and to cyclosporine in preventing transplant rejection. In all cases, plasma concentration measurements obtained and scrutinized during the early treatment stages enable the physician to avoid toxic plasma concentrations. In many cases, drug toxicity can be diagnosed clinically. For example, it is relatively easy to recognize acute phenytoin toxicity, and measuring the plasma concentration may not be necessary for diagnosis, although it may be helpful in adjusting the dosage subsequently. On the other hand, digoxin toxicity may mimic certain symptoms of heart disease, and measuring the plasma concentration in cases in which toxicity is suspected may be helpful in confirming the diagnosis. In a study by Aronson and Hardman [20], measurement of the plasma digoxin concentration in 260 patients treated with digitalis lanata preparations (digoxin, lanatoside C, betamethyl-digoxin) enabled the monitoring of certain outcomes that would not be apparent otherwise. Notably, the important overlap between "toxic" and "nontoxic" plasma concentration values limits use of the method in the diagnosis of digitalis toxicity (Fig. 2) [20]. However, in digitalis-treated patients with toxicity associated with digitalis plasma concentrations under 2.0 ng/mL, the method can detect digitalis sen-sitivity. Aronson and Hardman [20] determined that a dosage selection based on plasma drug concentration assessment led to a decrease of digitalis toxicity to below 4%. This method is not yet widely available. Thus, it should be noted that plasma digoxin concentration measurements should be obtained and evaluated in digitalis-treated patients with borderline renal function, in aged subjects, and in patients with rapid atrial fibrillation who require higher digitalis doses for heart rate control (Fig. 3) [21].
Fully revised, this accessible, practical text on pharmacokinetics for the non-specialist simplifies the complex subject matter with the use of clear diagrams and equations. Comprised of articles published in the Australian Prescriber, the book adopts a physiological approach, with direct application of the concepts to practical issues related to drug therapy. Self-assessment questions are included in each chapter.
Overview:
Pharmacokinetics Made Easy presents a complex subject in a simple, easy-to-understand manner. It is suitable for a wide audience including medical practitioners, health professionals and students. The individual chapters were initially published as a series of articles in Australian Prescriber to assist practitioners in drug dosing and therapy. The physiological approach adopted in this bestselling book addresses clinical issues in drug therapy and makes them directly applicable to practice situations.
In 2016, NIH launched a multi-faceted effort to enhance its stewardship over clinical trials. The goal of this effort is to encourage advances in the design, conduct, and oversight of clinical trials while elevating the entire biomedical research enterprise to a new level of transparency and accountability. The NIH definition of a clinical trial was revised in 2014 in anticipation of these stewardship reforms to ensure a clear and responsive definition of a clinical trial. Learn more about why NIH has made changes to improve clinical trial stewardship.
An increasing number of mice with genetic variation of intestinal transfer properties is becoming available. A luminal perfusion system for small intestinal segments, therefore, was adapted for the use in mice and rat pups to investigate longitudinal differences in intestinal drug and toxin transfer and to explore the adaptation of transfer properties during maturation under standardized conditions in vitro. At present, cell cultures are inadequate for this goal. The perfusator consists of an upper reservoir and a lower moist chamber to accommodate the intestinal segment. The luminal perfusion fluid is oxygenized and circulated by a gas lift. It is directed through the segment by two three-way taps. For safe and easy decontamination of radioactive substrates, the system is made entirely of glass. To perfuse fragile segments from small animals such as mice and rat pups in vitro, the perfusion pressure had to be reduced to 15 cm H2O column. Therefore, the design of the perfusator was changed, and the gas lift and the three-way taps were moved to the side. With segments from adult rats, the modified perfusor yielded the same transfer data for 59Fe, glucose, and water as did the standard device. Experiments with proximal and distal segments from mice and rat pups showed a longitudinal pattern of adaptation during maturation as well as due to iron deficiency that was in accordance with expectations extrapolated from literature.
All reviews of published articles are made public. This includes manuscript files, peer review comments, author rebuttals and revised materials. Note: This was optional for articles submitted before 13 February 2023.
The manuscript was written clearly in professional English, well organized and easy to follow. The authors are describing clear background of their purpose of study with proper references. All clear now with newly added supplemental files. Thank you for making the files.
The study design is clear; the authors investigated i) safety of oral glyburide, ii) pharmacokinetics of the drug after administration, and iii) estimate pharmacokinetic distribution in dogs with spontaneously occurred acute SCI. In addition the authors have added details of methods in this revised version.
This is a study of glyburide safety and pharmacokinetics in dogs with spinal cord injury. The manuscript is very well written with appropriate citations, the rational for the study is clear, the methods are appropriately detailed, the results are clearly presented, and the discussion lists appropriate caveats and shortcomings. I unequivocally endorse publication.
I encountered only a single difficulty that can be addressed with minor revision: in two instances, there is reference to "negative" canine plasma. It is unclear to me what the term negative implies here.
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This book is a valuable resource for veterinary students and a must-have for any house officer or emergency clinician. General practitioners will also benefit from the concise and accurate style as well as simple explanations of complex issues. In addition, the easy access to online information sheets will improve client compliance and understanding.
The first section pertaining to the basic principles of cancer biology and pathogenesis provides a useful foundation for general practitioners that will assist in addressing the questions most commonly asked by clients. Furthermore, the second and third sections that address diagnostic and therapeutic procedures can be dynamic in helping veterinarians educate clients prior to referral to a board-certified specialist. Finally, the fourth section provides information on specific malignancies and leads readers through each tumor type, similar to the approach used to evaluate a clinical patient. This approach is not only easy to follow but is clinically relevant.
Self-Assessment Colour Review of Rabbit Medicine and Surgery is a new addition to the Veterinary Self-Assessment Colour Review series. It attempts to cover all major categories from basic rabbit biology and husbandry to more advanced medicine and surgery. The material is provided in a problem-oriented, self-assessment format. Anesthesia, biology and husbandry, handling and restraint, infectious diseases, dermatology, cardiovascular and respiratory tract disease, ophthalmology, urinary tract, oral cavity-esophagus, gastrointestinal tract disease, metabolic disease, reproductive tract disease, musculoskeletal disease, and dental problems are covered in the book. This book will be easily enjoyed by beginning veterinary students to experienced veterinarians who have an interest in rabbit medicine and surgery. It is not a comprehensive textbook on the diagnosis and treatment of pet rabbits. The authors provide a variety of cases and diagnoses, which are often based on their personal experiences and not necessarily found in refereed literature. Each case is accompanied by a color photograph of the animal at time of initial examination or of a specific condition or lesion. Some pictures are not clear or informative in terms of what the authors are attempting to illustrate, but in general, images are of good quality. Descriptions are short, and the jump from initial examination to diagnosis in some may be a stretch for relative novices. Some cases primarily provide a physiology lesson rather than a discussion on a disease condition. Generally, the material is easy to understand and extremely informative.
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