Drug Distribution in Obesity and following Bariatric Surgery: A Literature Review

Background: The pharmacokinetic variables of drug clearance and volume of distribution are usually corrected for body weight or surface area. Only recently have the relationships which exist between body size, physiologic function and pharmacokinetic variables been evaluated in the obese population. These effects are not widely known, and data on this and the effects of bariatric surgical procedures are scantily documented in the surgical literature. Methods: Literature review. Results: Drugs with a low or moderate affinity for adipose tissue have a moderate increase in the volume of distribution (Vd), and this correlates with the increase in lean body mass (LBM). Highly lipophilic drugs, with some exceptions, show the expected increase in Vd and prolongation of elimination half-life, indicating a marked distribution into adipose tissue. Drug absorption, in general, is slowed by delayed gastric emptying and is normal when gastric emptying is normal or increased. Most drug absorption occurs in the small intestine where duration of drug/mucosal contact is the most important factor. Conclusions: Drugs whose distribution is restricted to LBM should utilize a loading dose based on ideal body weight (IBW). For those drugs which distribute freely into adipose tissue, the loading dose should be based on total body weight (TBW). Adjustment of the maintenance dose depends on clearance rates. In a few cases dosage adjustment depends on pharmacodynamic data, since drug clearance does not conform to these recommendations, for reasons which remain to be defined. Following bariatric surgery, in the absence of delayed gastric emptying or uncontrolled diarrhea, drug absorption rates are usually comparable to the non-operated patient.     

Receipt of specialty eye care by children.

BACKGROUND: No nationally representative data are available regarding use of eye care services by children. OBJECTIVES: To determine the proportion of children who receive specialty eye care and to evaluate the association of such care with age and other factors associated with health care utilization. METHODS: We used the 2000 National Health Interview Survey to estimate the proportion of nonblind children who received eye care in the preceding 12 months. The association between eye care and the factors of interest among children aged 6-17 years was measured through adjusted bivariate comparisons and logistic regression modeling. RESULTS: Eye care was received in the preceding 12 months by an estimated 7.3% (95% confidence interval [CI] 6.0-8.6) of the 22.8 million children aged 0-5 years and 24.8% (95% CI 23.5-26.2) of the 48.5 million children aged 6-17 years. Among children aged 6-17 years, girls had 29% greater odds than boys to have received eye care (P=.001). Among children <200% of the federal poverty level, those with public health insurance had greater odds of receiving eye care than did uninsured children or those with private health insurance (P<.001). Among children >200% of the federal poverty level, uninsured children had lower odds than did children with public or private health insurance (P<.004) to receive eye care. Well-child care was associated with increased eye care utilization among children aged 12-14 years (P<.001). CONCLUSIONS: Receipt of specialty eye care is common and increases with age. However, there are marked variations among school-aged children. Future studies should address the causes and effects of these findings.     

A Cost-Effective and Rational Surgical Approach to Patients With Snoring,Upper Airway Resistance Syndrome,or Obstructive Sleep Apnea Syndrome

The past decade has seen several innovations in the surgical techniques available for treatment of patients with sleep-disordered breathing. Outpatient techniques such as laser-assisted uvulopalatoplasty (LAUP) and more aggressive procedures designed to address hypopharyngeal and base of tongue obstruction (genioglossus advancement and hyoid myotomy) have been developed and proven successful. We describe the efficacy of LAUP for snoring (72.7%), upper airway resistance syndrome (81.8%), and mild (mean[±SD] respiratory disturbance index [RDI] = 12 ± 8.1) obstructive sleep apnea (41.7%) in 56 patients who underwent 132 LAUP procedures in a 26-month period. Thirty-two patients with more significant obstructive sleep apnea (mean RDI = 41.8 ± 23.1) underwent multilevel pharyngeal surgery consisting of genioglossus advancement and hyoid myotomy combined with uvulopalatopharyngoplasty. The surgical success rate in this group of patients was 85.7% when commonly accepted criteria were applied. We recommend a stratified surgical approach to patients with sleep-disordered breathing. Progressively worse airway obstruction marked by multilevel pharyngeal collapse and more severe sleep-disordered breathing is treated with incrementally more aggressive surgery addressing multiple areas of the upper airway.     

Identification of a novel pulmonary oedema producing toxin from Indian red scorpion (Mesobuthus tamulus) venom.

The experiments were conducted to identify the toxin that produces pulmonary oedema in Mesobuthus tamulus (BT) envenomed animals. Crude BT venom was subjected to Sephadex gel filtration (G-75) and the fractions were screened for optical density (OD), neurotoxicity (prolongation of compound action potential in frog sciatic nerve) and lethality. All these parameters exhibited a peak between 54-94 ml eluates. Fractions of this peak were pooled (SP) and loaded on to carboxymethyl cellulose column. The column was then eluted with increasing buffer concentrations at constant pH and temperature. Eluates were screened for neurotoxicity and OD. Four peaks of neurotoxic activity (T1-T4) were detected. T2 and T3 were lethal whereas T1 and T4 were non-lethal. T2 exhibited mainly neurotoxicity and failed to augment phenyldiguanide (PDG)-induced reflex response or to produce pulmonary oedema. T3 was having minimal neurotoxic actions but augmented PDG-reflex and produced pulmonary oedema. The effects of T3 persisted even after dialysis with 8 kDa cut-off filter but not those of T2. The T3 effects resembled toxic manifestations of BT venom and were blocked by aprotinin pre-treatment. T3 demonstrated a band at approximately 100 kDa in SDS-PAGE. The results demonstrate the presence of a lethal, high molecular weight, pulmonary oedema producing toxin in BT venom.     

Comparative preclinical and clinical pharmacokinetics of a cremophor-free, nanoparticle albumin-bound paclitaxel (ABI-007) and paclitaxel formulated in Cremophor (Taxol).

PURPOSE: To compare the preclinical and clinical pharmacokinetic properties of paclitaxel formulated as a Cremophor-free, albumin-bound nanoparticle (ABI-007) and formulated in Cremophor-ethanol (Taxol). EXPERIMENTAL DESIGN: ABI-007 and Taxol were given i.v. to Harlan Sprague-Dawley male rats to determine pharmacokinetic and drug disposition. Paclitaxel pharmacokinetic properties also were assessed in 27 patients with advanced solid tumors who were randomly assigned to treatment with ABI-007 (260 mg/m(2), 30 minutes; n = 14) or Taxol (175 mg/m(2), 3 hours; n = 13), with cycles repeated every 3 weeks. RESULTS: The volume of distribution at steady state and clearance for paclitaxel formulated as Cremophor-free nanoparticle ABI-007 were significantly greater than those for paclitaxel formulated with Cremophor (Taxol) in rats. Fecal excretion was the main elimination pathway with both formulations. Consistent with the preclinical data, paclitaxel clearance and volume of distribution were significantly higher for ABI-007 than for Taxol in humans [21.13 versus 14.76 L/h/m(2) (P = 0.048) and 663.8 versus 433.4 L/m(2) (P = 0.040), respectively]. CONCLUSIONS: Paclitaxel formulated as ABI-007 differs from paclitaxel formulated as Taxol, with a higher plasma clearance and a larger volume of distribution. This finding is consistent with the absence of paclitaxel-sequestering Cremophor micelles after administration of ABI-007. This unique property of ABI-007 could be important for its therapeutic effectiveness.