Given a passage with a context and an answer, construct a question on the basis of the information present in the passage. Construct the question in such a way that (i) it is unambiguous, (ii) it is answerable from the passage, (iii) its answer is unique (iv) it answer uses text phrases from the passage. Avoid creating questions that (i) can't be answered correctly without actually understanding the passage and (ii) uses the same words or phrases given in the passage.

Context: Isotretinoin is effective in the treatment of severe acne and rosacea. Both parent drug and its main metabolite 4-oxo-isotretinoin are potentially teratogenic compounds and contain a carboxylic acid moiety. In the presence of ethanol, naturally occurring as well as synthetic retinoids also containing a carboxylic acid moiety are capable of undergoing an ethyl esterification with the metabolic formation of more lipophilic compounds with a much longer terminal half-life.', 'To determine if isotretinoin (13-cis-RA), its main metabolite 4-oxo-isotretinoin (4-oxo-13-cis-RA), and other possible metabolites in the presence or absence of ethanol are converted to their corresponding ethyl derivatives in patients with severe acne or rosacea after multiple isotretinoin dosing. In addition, pharmacokinetic parameters of the parent drug and its 4-oxo metabolite were determined.', 'Eleven patients with severe acne or rosacea were treated with isotretinoin daily for 3 months and investigated pharmacokinetically during 24 h after 1 month of treatment and for up to 28 days after discontinuation of therapy. A possible influence of ethanol was evaluated using a simple self-administered questionnaire and by measuring serum ethanol levels during treatment. The concentrations of isotretinoin, 4-oxo-isotretinoin and possible ethylated and nonethylated metabolites were measured by reverse-phase high-performance liquid chromatography.', "Although seven of 11 patients had a considerable weekly alcohol intake, no endogenous synthesis of ethyl derivatives of isotretinoin, the main 4-oxo metabolite or the all-trans compounds was chromatographically detectable in any of the patients' plasma samples during the treatment period. Multiple dose pharmacokinetic data for the parent drug and its main metabolite were comparable to previous studies.
Answer: The metabolism and pharmacokinetics of isotretinoin and its main metabolites are not influenced by ethanol during long-term isotretinoin treatment. After ceasing long-term isotretinoin therapy the recommended period of 1 month for using anticonceptive measures in fertile women seems adequate.
Are the metabolism and pharmacokinetics of isotretinoin in patients with acne and rosacea influenced by ethanol?

Context: Cells of the myeloid lineage comprise a very heterogeneous population with many phenotypes and functional activities including macrophages and dendritic cells. To investigate the status, differentiative potential and lineage commitment of monocytic cells in systemic lupus erythematosus (SLE) patients, this study isolated and cultured peripheral blood monocytes from patients and healthy donors.', 'Monocytes were isolated by gradient centrifugation and adherence to plastic dishes. The cells were then cultured for three days, partially supplemented with GM-CSF and interleukin 4 (IL4) to obtain dendritic cells. The differentiation status was monitored by the expression of surface markers using flow cytometry and cytokine secretion.', 'Monocytes from SLE patients expressed significantly lower numbers of the monocytic marker CD14 and HLA-DR while secreting significantly more tumour necrosis factor alpha (TNFalpha) than monocytes from healthy donors. The addition of GM-CSF and IL4 resulted in an inhibition of TNFalpha secretion, but was not sufficient to generate monocytederived dendritic cells.
Answer: Monocytes from SLE patients are severely altered in phenotype and function and have a limited differentiation flexibility towards the accessory type of monocytic cells.
Are monocytes from systemic lupus erythematous patients severely altered in phenotype and lineage flexibility?

Context: Evidence obtained from porcine cell cultures and experiments in laboratory animals indicates that transmembrane transporters may play a role in the distribution of the active morphine metabolite morphine-6-glucuronide (M6G). This was evaluated in a study in healthy volunteers.', 'Ten subjects received an intravenous M6G infusion for 30 min at a dosage of 0.5 mg/kg body weight, leading to M6G plasma concentrations approximately two to three times higher than those observed with analgesic morphine doses in subjects with normal kidney function. In a randomized, double-blind, three-way crossover fashion, subjects received 800 mg quinidine for inhibition of P-glycoprotein; 500 mg probenecid for inhibition of other transporters, including organic anion transporter peptide, multidrug resistance-related protein, and organic anion transporter families; or placebo 1 h before the start of M6G administration. Plasma concentrations of M6G and pupil size were measured for 7 h.', 'Probenecid pretreatment resulted in a decrease in the clearance of M6G from 8.3 +/- 1 l/h to 6.7 +/- 1.3 l/h (factor of 0.8; P < 0.05 vs. placebo cotreatment). This was paralleled by an increase by a factor of 1.2 of the area under the miotic effect-versus-time curves (P < 0.05 vs. placebo). In contrast, quinidine pretreatment had no influence on the pharmacokinetics of M6G.
Answer: The active morphine metabolite is subject to transmembrane transport by transporters inhibited by probenecid in humans.

Does probenecid interact with the pharmacokinetics of morphine-6-glucuronide in humans?