Browse every published article, from the latest research to earlier analysis. Use the page numbers below to explore the complete archive.
A drug’s oral bioavailability is the fraction of an oral dose that reaches the systemic circulation. In a 2018 midazolam modeling study, that fraction was estimated to be substantially higher in preterm neonates than the adult value discussed by the authors. Developmental changes in metabolism were central to the explanation. What the investigators modeled Brussee…
A percentage expressed relative to baseline can be easy to misread. In a plasma-exchange case, a clobazam result of 75% of baseline describes a concentration about 25% below baseline. What the serial samples showed The report followed a patient with refractory status epilepticus through two exchange sessions. In one session, total serum clobazam fell from…
A fasting-related change in drug exposure can arise through absorption or through removal from the circulation. A crossover study separated these questions by testing oral and intravenous drug probes after different fasting periods. What the study compared Twelve healthy adults received a probe cocktail after an overnight fast and after 36 hours of fasting. The…
A drug solution can retain its measured concentration while a separate question remains about microbial contamination. A syringe-storage study examined chemical stability and explicitly separated that finding from sterility. What the experiment measured The investigators stored selected single-drug formulations in polypropylene syringes at room temperature. They measured concentrations initially, near day 50, and at day…
A urine screening study reported overall agreement from 92.4% to 100% between an immunoassay and a mass-spectrometry method. To interpret that range, examine the positive and negative specimens available for each drug. Which comparisons were possible? The study tested 105 urine specimens. Some drug classes had discordant results. For cocaine, methadone and phencyclidine, no positive…
A repeated-measures study can ask whether treatment groups differ on average and whether they follow different trajectories over time. These are separate statistical questions. A randomized anesthesia study reported both. What the measurements showed Seventy-two women undergoing gynecologic laparoscopic surgery received one of three anesthetic regimens. Researchers recorded regional cerebral oxygen saturation at four stages,…
A receptor’s subunit composition can influence how it responds to both its natural transmitter and a drug. Researchers examined that relationship by expressing selected human GABA-A receptor combinations in frog egg cells and measuring electrical currents. What the receptor experiment isolated The team varied the epsilon, theta and gamma-2 subunits in receptors containing alpha-3 and…
A study comparing sedation with and without preventive phenylephrine used two ways to identify low blood pressure. Both the starting pressure and the lowest recorded value therefore matter to its outcome. The study combined an absolute and a relative threshold Hypotension meant a systolic pressure below 90 mmHg or a decrease of more than 20%…
A dose-response model can return an estimate beyond the doses used in an experiment. The confidence interval and observed data help show how much support that estimate has. What the remimazolam study tested One hundred patients were randomized to five single intravenous doses between 0.2 and 0.6 mg/kg. For the endpoint BIS at or below…
CBD and its acidic precursor, CBDA, can be measured separately. Their ratio describes part of a product’s chemistry, but several factors can produce a high or low value. A study of 40 commercial hemp products illustrates the range. What the product testing found Using a validated liquid chromatography–mass spectrometry method, researchers found that many products…
A pharmacokinetic model can fit much of a concentration–time curve and still depart from measurements during a particular interval. A study modeling the interaction between itraconazole and midazolam examined that kind of discrepancy. What the investigators modeled The researchers used baseline data from 19 genotyped adult men to build linked models for midazolam and two…
A physiologically based pharmacokinetic model combines information about a drug with assumptions about physiology. Researchers used this approach to estimate how isavuconazole might interact with other drugs in children when direct interaction data were limited. How the model used clinical data The team built and checked the isavuconazole model against adult and pediatric pharmacokinetic data.…
The bispectral index (BIS) summarizes features of the electroencephalogram. The Modified Observer’s Assessment of Alertness/Sedation scale scores a patient’s response to stimulation. A prospective study compared these measures during the first five minutes of induction with remimazolam and sufentanil. Correlation and agreement answer different questions The measures showed a moderate correlation early in induction, which…
A simulated digestion test measures how much cannabidiol a formulation releases into a test fluid. A pharmacokinetic experiment measures what reaches the circulation. Nie and colleagues used both methods to compare two carriers made from zein, a corn protein. What the test fluids revealed After two hours in simulated gastric fluid, the modified zein particles…
An alveolar breath measurement can show that a volatile chemical is present in exhaled air. That does not necessarily reveal how the chemical entered the body. A historical review illustrates the distinction with tetrachloroethylene, a solvent used in dry cleaning and degreasing. What the skin-exposure experiment observed Hake and Stewart reviewed an experiment in which…
A laboratory can describe the terpenoids in cannabis when it tests the sample. Inferring the original profile also requires information about whether the material was stored whole or ground, how long it was stored, and at what temperature. What the storage experiment compared Milay and colleagues stored whole and ground flowers from THC-rich and CBD-rich…
When a drug is present at low concentration, the way a mass spectrometer produces ions can affect how readily the lab can measure it. A 1980 study compared positive and negative methane chemical ionization for several benzodiazepines and applied the negative-ion approach to nordiazepam. Why the researchers changed ionization mode For some of the compounds,…
The dose chart and the plasma result describe different parts of midazolam exposure. In a prospective ICU study, patients receiving venovenous extracorporeal membrane oxygenation (ECMO) received more midazolam by weight than patients on conventional respiratory support. The concentration results did not follow the same pattern for the parent drug and its metabolites. Compare the dose,…
A hemp extract contains compounds besides the cannabinoids a lab wants to measure. When those co-extracted compounds change the analytical response, standards made in clean solvent can give the wrong relationship between signal and concentration. Matrix-matched calibration starts with a material that resembles the sample and has had the target compounds removed. How the researchers…
In a cannabis extract, the major cannabinoids can be present at concentrations far above the minor compounds. One dilution can bring an abundant analyte into the instrument’s calibration range while pushing a minor analyte below the level the method can quantify. What the validation measured McRae and Melanson coupled LC–MS/MS with a broad calibration range…
A patient evaluated for apparent alcohol withdrawal had a bupropion concentration of 133 ng/mL and a hydroxybupropion result reported as greater than 3,000 ng/mL. The two measurements tell different parts of the toxicology story. A lower bound for the metabolite The parent drug was below the reporting laboratory’s toxic threshold. The metabolite exceeded its own…
A diazepam standard in clean solvent can respond differently from the same amount of diazepam in a seafood extract. Other compounds that reach the mass spectrometer at the same time can suppress or enhance ionization. The practical question is whether the sample cleanup makes that difference small enough to use solvent calibration. How the researchers…
Measuring the parent drug alone can understate an exposure change when a metabolite is also active. A phase 1 study of an investigational IV rifabutin formulation illustrates the distinction. What changed with itraconazole The researchers studied rifabutin and its active metabolite, 25-O-desacetyl rifabutin, after BV100 administration in healthy participants. With itraconazole, rifabutin area under the…
Discovering an unexpected compound and measuring it routinely are separate laboratory tasks. In a fish-tissue study, investigators used different mass spectrometry workflows for the two jobs. From an unexpected peak to a named compound High-resolution screening found a peak that shared nordiazepam’s precursor mass but eluted later and fragmented differently. Comparison with a reference standard…
Enzyme measurements from a laboratory model and clearance measured in a living subject support different parts of a pharmacokinetic argument. What the researchers measured Nicoli and colleagues found changes in P450-related gene expression and reduced activity in several enzyme assays in mice lacking functional Npc1. They also used midazolam as a probe in living mice…
When a drug is swallowed, intestinal metabolism can change how much reaches the bloodstream. An IV dose bypasses that first step, which can help distinguish an intestinal interaction from an effect on systemic clearance. What the route comparison found The review describes a crossover study in 16 healthy volunteers. With simeprevir, the oral midazolam area…
An oral adsorbent can interact with another drug inside the gastrointestinal tract. The amount of opportunity depends partly on how quickly the other product dissolves and how quickly drug leaves the gut by absorption. What went into the model Koya and colleagues estimated dissolution and absorption for 68 drugs at six dosing intervals. They compared…
When a patient is already receiving a continuous IV infusion, measuring the parent drug in blood ordinarily blends that exposure with any oral dose. A labeled tracer can distinguish the oral contribution. What the researchers measured Investigators gave a single oral carbon-14 midazolam microtracer to 46 clinically stable children in intensive care who were receiving…
Interaction models often need an estimate of the drug concentration available to inhibit an enzyme. When almost all of the drug is bound to plasma proteins, small uncertainty in the unbound fraction can matter. What the researchers entered in the calculation Cannady and colleagues reported that evacetrapib’s unbound fraction in human plasma was below 0.1%…
Finding two drugs in serum does not necessarily point to two products. Knowing the ingredients of the material recovered at the scene can change how a toxicologist interprets the pair. What the case record contained The patient arrived with profound central nervous system depression. A rapid urine screen detected barbiturates and benzodiazepines. Subsequent serum testing…