A comparison of drug protein binding and alpha 1‐acid glycoprotein concentration in Chinese and Caucasians.

Feely, J.; Grimm, Terry

doi:10.1111/j.1365-2125.1991.tb05579.x

Cited by 25 publications

(19 citation statements)

References 9 publications

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“…Whether these findings represent a genuine ethnic difference is uncertain, but they appear to have little effect on the pharmacodynamic responses. In Chinese, levels of circulating al-acid glycoprotein are 25% lower than in Caucasians and this has been implicated in higher plasma concentrations of, and sometimes increased sensitivity to, certain basic drugs in this racial group [2,10]. Neither perindopril nor perindoprilat are basic drugs and so are mainly bound to albumin, the levels of which were found to be virtually the same in the two groups (see Table 3).…”

Section: Discussionmentioning

confidence: 99%

Comparison of the pharmacokinetics and pharmacodynamics of oral doses of perindopril in normotensive Chinese and Caucasian volunteers.

Critchley

Tomlinson

Resplandy

1995

Brit J Clinical Pharma

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1. The pharmacokinetics of perindopril and perindoprilat and the hormonal and haemodynamic responses following a single oral dose were studied in 12 Chinese and 10 Caucasian healthy, normotensive volunteers on two occasions. Perindopril was given on the first occasion as a 4 mg dose and then after at least 10 days as a weight‐adjusted dose of 4 mg/70 kg. Plasma was sampled for assay of perindopril, perindoprilat, plasma renin activity (PRA), aldosterone, angiotensin I (AI) and ACE activity. Urine was collected for perindopril and perindoprilat assay. A radioimmunoassay technique was used to measure the prodrug and its active metabolite. 2. The time to maximum concentration (tmax) for perindopril was shorter for the Chinese group after the 4 mg dose (median 0.5, range 0.5‐1.5 h vs median 1.0, 0.5‐1.5 h P < 0.05) and also tended to be shorter after the weight‐adjusted dose (median 0.5, range 0.5‐1.0 h vs median 1.0, range 0.5‐3.0 h). Cmax and AUC tended to be higher after the 4 mg dose in the Chinese group who had a lower body weight than the Caucasians. 3. The tmax of perindoprilat tended to be shorter for both doses and there was a tendency towards a higher Cmax after the 4 mg dose in the Chinese group but there was no statistically significant difference between the two groups. 4. There were no differences in the levels of PRA, plasma AI, plasma aldosterone or the degree of ACE‐inhibition for either dose in the two ethnic groups. 5. Blood pressure was measured at intervals up to 24 h post‐dose in both the supine and standing positions. Perindopril reduced blood pressure acutely with respect to the pre‐dose level with good tolerability in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Discussionmentioning

confidence: 99%

Comparison of the pharmacokinetics and pharmacodynamics of oral doses of perindopril in normotensive Chinese and Caucasian volunteers.

Critchley

Tomlinson

Resplandy

1995

Brit J Clinical Pharma

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“…To develop such dosing regimens, detailed knowledge of the antibiotic's PK is required. A number of physiological differences have been identified between ethnic groups that can significantly affect the PK of drugs, such as body size, body fat percentage, hepatic metabolism, biliary excretion, renal secretion and alpha1-acid glycoprotein (AGP) concentration (9)(10)(11)(12)(13)(14)(15)(16). Unfortunately, despite optimisation of antibiotic administration in accordance with its PK/PD properties being an important clinical determinant (8,17), there are currently no antibiotic PK data available for the Indigenous population to guide treatment therapies, let alone for severely septic patients that can anticipate drastic PK alterations (18,19).…”

Section: Overviewmentioning

confidence: 99%

“…Early antibiotic therapy is the cornerstone of treatment of sepsis and is associated with increased survival (14,(31)(32)(33). Moreover, there is growing evidence which demonstrates the optimisation of antibiotic dosing in accordance with its PK/PD profile increases clinical cure rates and reduces mortality, especially in severely septic patients (6,7,(34)(35)(36)(37).…”

Section: Antibiotic Pk/pdmentioning

confidence: 99%

“…AGP is the second most important drug-binding plasma protein after albumin and has high affinity for basic and neutral drugs (251)(252)(253) less AGP than Caucasians, whereas no interethnic differences have been reported in these subjects for albumin (14,16,23,115,258). For AGP-bound drugs, an increased unbound drug fraction is observed in populations with lower AGP concentration and this increase in unbound drug available for distribution around the body leads to an overall increase in V d and CL (14,23,115,253).…”

Section: Antibacterial Physicochemical Characteristics -Hydrophilicitmentioning

confidence: 99%

“…For AGP-bound drugs, an increased unbound drug fraction is observed in populations with lower AGP concentration and this increase in unbound drug available for distribution around the body leads to an overall increase in V d and CL (14,23,115,253).…”

Section: Antibacterial Physicochemical Characteristics -Hydrophilicitmentioning

confidence: 99%

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Improving antibiotic dosing in critically ill Australian Indigenous patients with severe sepsis

Tsai¹

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Sepsis is a major health issue in the Australian Indigenous population. Unfortunately, the high rates of mortality and morbidity caused by sepsis or severe sepsis in this population have not significantly reduced over recent decades. Research into the role of optimisation of antibiotic therapy for improving patient outcomes is certainly an important area of need. In other patient populations, there is increasing evidence of an improvement of clinical cure rates and survival in patients with severe sepsis when antibiotic dosing results in therapeutic concentrations, that is, achieves pharmacokinetic/pharmacodynamic (PK/PD) targets. However, numerous PK changes caused by the altered physiology associated with critical illness may reduce the likelihood of such effective dosing.Previous studies have identified a number of physiological characteristics in the Australian Indigenous population which suggest that interethnic PK differences are likely in comparison with the non-Indigenous. As most PK data of antibiotics were obtained from healthy Caucasian volunteers, whether these data can be extrapolated to the critically ill Indigenous patients requires investigation.The aims of this thesis are to describe the PK of meropenem, ceftriaxone, vancomycin and piperacillin in severely septic Indigenous patients; compare the PK with existing data from nonIndigenous patients; design optimised dosing regimens for each of the study antibiotics; and quantify the variation in renal function of critically ill Indigenous patients. This thesis consists of nine Chapters:Chapter one provides an overview of the current clinical challenges encountered in antibiotic dosing in critically ill patients. It also discusses specific physiological characteristics of Australian Indigenous patients which may lead to different PK compared with non-Indigenous comparators.Chapter two comprises of a narrative review which discusses the PK/PD factors that should be considered when prescribing antibiotics to critically ill patients. This Chapter summarises data which describe an improvement in clinical outcome when antibiotics achieve PK/PD targets. ThisChapter concludes to support an individualised approach to dosing antibiotics as opposed to the 'one dose fits all' approach that is common to clinical practice.ii Chapter three incorporates a systematic review which investigates the published data describing differences in antibiotic PK between different ethnic groups. No reports on PK in Indigenous Australians were found. The predominant data described differences in PK between the Asian and Caucasian ethnicities. Typically, Asian subjects manifested higher antibiotic concentrations for antibiotics that have significant hepatic metabolism, are substrates to p-glycoprotein or other forms of active transport and/or have high alpha-1-acid glycoprotein binding.Chapter four incorporates a study which described the renal function of critically ill Australian Indigenous patients. This study found a numerically higher incidence of augmented renal clea...

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Pharmacodynamics

Triggle¹

2000

Kirk-Othmer Encyclopedia of Chemical Technology

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Pharmacodynamics is the study of drug action primarily in terms of drug structure, sites of action, mechanisms of drug–target interaction, as well as the biochemical and physiological consequences of the action of the drug. Pharmacodynamics may be regarded as one branch of the larger discipline of pharmacology relating to all aspects of drug action, from isolation, characterization, to pharmacokinetic, therapeutic, and toxicologic descriptions. A principal concern of pharmacodynamics is the interaction of drugs with specific receptors. Increasingly, these studies are quantitative ones relating structural and genetic information. Such studies include the description of binding interactions, the definition of structure–activity relationships, the elucidation of transduction mechanisms by which receptor signals are translated into response, and the mechanisms by which receptors are regulated through chronic drug and hormone action as well as during disease processes. These considerations of pharmacodynamics are exerted at both preclinical and clinical states.

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A comparison of drug protein binding and alpha 1‐acid glycoprotein concentration in Chinese and Caucasians.

Cited by 25 publications

References 9 publications

Comparison of the pharmacokinetics and pharmacodynamics of oral doses of perindopril in normotensive Chinese and Caucasian volunteers.

Comparison of the pharmacokinetics and pharmacodynamics of oral doses of perindopril in normotensive Chinese and Caucasian volunteers.

Improving antibiotic dosing in critically ill Australian Indigenous patients with severe sepsis

Pharmacodynamics

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