Interpatient variability

West WL et al. Interpatient variability genetic predisposition and other genetic factors. J Clin Pharmacol 1997 37 635-648. 

Cardiovascular and respiratory parameters should be monitored continuously (see Table 12-1). Trends, rather than specific CVP or PAOP numbers, should be monitored because of interpatient variability in response. 

Because of large interpatient variability in theophylline clearance, routine monitoring of serum theophylline concentrations is essential for safe and effective use. A steady-state range of 5 to 15 mcg/mL is effective and safe for most patients. 

Methylxanthines are no longer considered first-line therapy for COPD. Inhaled bronchodilator therapy is preferred over theophylline for COPD because of theophylline s risk for drug interactions and the interpatient variability in dosage requirements. Theophylline may be considered in patients who are intolerant or unable to use an inhaled bronchodilator. A methylxanthine may also be added to the regimen of patients who have not achieved an optimal clinical response to an inhaled anticholinergic and [i2-agonist. 

Comparison of Equafion 18.33 wifh Equation 18.29 shows that a is ln(EC5o) x is In C, and p corresponds to the Hill coefficient, h, which now represents interpatient variability. 

Probably not, but very wide interpatient variability 2 3% of Caucasians 15 25% of Orientals 4% of Blacks 5 8% of Caucasians Lower in other races... 

In psychopharmacology, interest in the properties of enantiomers has been aided by the need to improve the therapeutic efficacy and decrease the side effects and toxicity of drugs. For example, if the therapeutic activity resides entirely in one enantiomer (called a eutomer) then giving a racemic mixture which contains the active and the inactive enantiomer is clearly wasteful. Thus using the single enantiomer (isomer or eutomer) should enable the dose of the drug to be lowered, reduce the interpatient variability in the response and, hopefully, reduce the side effects and toxicity of the drug (see Table 3.4). 

Reduction in the interpatient variability in metabolism and in response to treatment. 

Most opioid analgesics are well absorbed when given by subcutaneous, intramuscular, and oral routes. However, because of the first-pass effect, the oral dose of the opioid (eg, morphine) may need to be much higher than the parenteral dose to elicit a therapeutic effect. Considerable interpatient variability exists in first-pass opioid metabolism, making prediction of an effective oral dose difficult. Certain analgesics such as codeine and oxycodone are effective orally because they have... 

For most antimicrobial agents, the relation between dose and therapeutic outcome is well established, and serum concentration monitoring is unnecessary for these drugs. To justify routine serum concentration monitoring, it should be established (1) that a direct relationship exists between drug concentrations and efficacy or toxicity (2) that substantial interpatient variability exists in serum concentrations on standard doses (3) that a small difference exists between therapeutic and toxic serum concentrations (4) that the clinical efficacy or toxicity of the drug is delayed or difficult to measure and (5) that an accurate assay is available. 

Hellriegel ET, Bjornsson TD, Hauck WW. Interpatient variability in bioavailability is related to the extent of absorption implications for bioavailability and bioequivalence studDfei Pharmacol Ther, 1996 ... 

Consequently, the newer NSAIDs have not always been shown to be clinically superior to aspirin, but some agents may provide better effects in some patients. Considering the interpatient variability in drug response, there are surely cases in which another NSAID will produce better therapeutic effects with... 

During the course of clinical development, it is often important to identify the structures of metabolites. This information provides an opportunity to better understand interpatient variability in pharmacokinetics and toxicity. Clinical studies performed by Lokiec and coworkers, 1996 on a semisynthetic derivative of 20(S)-camptothecin, CPT-11, demonstrate the use of LC/MS to investigate the in vivo metabolic pathways. CPT-11 is a potent inhibitor of topoisomerase II, which is an enzyme involved in DNA duplication, and exhibits significant activity against various types of tumors in clinical studies. The understanding and control of the main biotransformation pathways are particularly important for anticancer drugs because therapeutic doses are often close to the maximum tolerated dose. 

Dasatinib interpatient and inter-occasion variability is important and ranges from 32 to 118 %. A substantial proportion of the inter-occasion variability is supposedly related to the drug bioavailability. The origin of the interpatient variability has not been elucidated yet, but is presumably related to dasatinib CYP3A-mediated metabolism, characterized by high variability in activity and expression [46],... 

Sunitinib interpatient variability in pharmacokinetics is also significant, of approximately 40 %, which is unexplained yet [47],... 

Sorafenib pharmacokinetics shows a large interpatient variability [49, 57], The large interpatient variability is supposed to be the result of slow dissolution of the drug in the gastrointestinal tract and of the existence of an entero-hepatic circulation [51],... 

Wilkinson GR. Prediction of interpatient variability of drug metabolizing ability. In Wilkinson GR, Rawlins MD, eds. Drug Metabolism and Disposition Considerations in Clinical Pharmacology. Lancaster, PA MTP Press, 1985, 183-209. 

The full model can reproduce all the systematic features of the absorption curves in Fig. 2.5 [11]. In the present form, the model does not account for the interpatient variability observed in Fig. 2.4 or for the nonsystemahc phenomena discussed in connection with Fig. 2.5. Ideally, in our mechanism-based modeling approach, any form of unsystematic variation in the experimental results should be given a separate explanation, i.e. specific studies should be undertaken to explain the observed variability in absorption rates and binding capacities. Statistical outliers should be considered as potential sources of new information. 

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